TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
AU  - Pilipović, Ivan
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1693
AB  - There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually diergic changes in thymopoietic efficiency, which in rodents occur around puberty and lead to a substantial phenotypic and functional remodeling of the peripheral T-cell compartment. This in turn leads to an alteration in the susceptibility to infection and various immunologically mediated pathologies. Our laboratory has explored interdependence in the programming and development of the hypothalamo-pituitary-gonadal axis and thymus using experimental model of neonatal androgenization. We have outlined critical points in the complex process of T-cell development depending on neonatal androgen imprinting and the peripheral outcome of these changes and have pointed to underlying mechanisms. Our research has particularly contributed to an understanding of the putative role of changes in catecholamine-mediated communications in the thymopoietic alterations in adult neonatally androgenized rats.
PB  - Humana Press Inc, Totowa
T2  - Immunologic Research
T1  - Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis
VL  - 52
IS  - 1-2
SP  - 7
EP  - 19
DO  - 10.1007/s12026-012-8278-6
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica and Pilipović, Ivan",
year = "2012",
abstract = "There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually diergic changes in thymopoietic efficiency, which in rodents occur around puberty and lead to a substantial phenotypic and functional remodeling of the peripheral T-cell compartment. This in turn leads to an alteration in the susceptibility to infection and various immunologically mediated pathologies. Our laboratory has explored interdependence in the programming and development of the hypothalamo-pituitary-gonadal axis and thymus using experimental model of neonatal androgenization. We have outlined critical points in the complex process of T-cell development depending on neonatal androgen imprinting and the peripheral outcome of these changes and have pointed to underlying mechanisms. Our research has particularly contributed to an understanding of the putative role of changes in catecholamine-mediated communications in the thymopoietic alterations in adult neonatally androgenized rats.",
publisher = "Humana Press Inc, Totowa",
journal = "Immunologic Research",
title = "Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis",
volume = "52",
number = "1-2",
pages = "7-19",
doi = "10.1007/s12026-012-8278-6"
}

Leposavić, G., Perišić, M.,& Pilipović, I.. (2012). Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis. in Immunologic Research
Humana Press Inc, Totowa., 52(1-2), 7-19.
https://doi.org/10.1007/s12026-012-8278-6

Leposavić G, Perišić M, Pilipović I. Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis. in Immunologic Research. 2012;52(1-2):7-19.
doi:10.1007/s12026-012-8278-6 .

Leposavić, Gordana, Perišić, Milica, Pilipović, Ivan, "Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis" in Immunologic Research, 52, no. 1-2 (2012):7-19,
https://doi.org/10.1007/s12026-012-8278-6 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Perišić, Milica
AU  - Leposavić, Gordana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1686
AB  - This paper highlights the multiple putative thymic and extrathymic points of intersection and interaction between glucocorticoids (GCs) and catecholamines (CAs)-the end-point mediators of the major routes of communication between the brain and the immune system-in the context of intricate thymic T cell-developmental tuning. More specifically, we discuss in detail findings indicating that adrenal GCs can influence thymopoiesis by adjusting directly and/or indirectly (through modulation of pituitary and local ACTH synthesis) not only thymic GC synthesis, in a cell type-specific manner, but also thymic CA bioavailability (via altering CA outflow from sympathetic nerve endings and local CA synthesis), beta and alpha(1)-adrenoceptor (AR) expression, and/or AR-mediated intracellular signal transduction in thymic cells. In addition, this short review points to GC-and CA-sensitive stages along the multistep T cell-developmental journey and the possible effects of altered GC, and consequently CA signaling, on thymopoietic efficiency.
PB  - Blackwell Science Publ, Oxford
T2  - Neuroimmunomodulation in Health and Disease I
T1  - Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network
VL  - 1261
SP  - 34
EP  - 41
DO  - 10.1111/j.1749-6632.2012.06623.x
ER  - 

@article{
author = "Pilipović, Ivan and Radojević, Katarina and Perišić, Milica and Leposavić, Gordana",
year = "2012",
abstract = "This paper highlights the multiple putative thymic and extrathymic points of intersection and interaction between glucocorticoids (GCs) and catecholamines (CAs)-the end-point mediators of the major routes of communication between the brain and the immune system-in the context of intricate thymic T cell-developmental tuning. More specifically, we discuss in detail findings indicating that adrenal GCs can influence thymopoiesis by adjusting directly and/or indirectly (through modulation of pituitary and local ACTH synthesis) not only thymic GC synthesis, in a cell type-specific manner, but also thymic CA bioavailability (via altering CA outflow from sympathetic nerve endings and local CA synthesis), beta and alpha(1)-adrenoceptor (AR) expression, and/or AR-mediated intracellular signal transduction in thymic cells. In addition, this short review points to GC-and CA-sensitive stages along the multistep T cell-developmental journey and the possible effects of altered GC, and consequently CA signaling, on thymopoietic efficiency.",
publisher = "Blackwell Science Publ, Oxford",
journal = "Neuroimmunomodulation in Health and Disease I",
title = "Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network",
volume = "1261",
pages = "34-41",
doi = "10.1111/j.1749-6632.2012.06623.x"
}

Pilipović, I., Radojević, K., Perišić, M.,& Leposavić, G.. (2012). Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network. in Neuroimmunomodulation in Health and Disease I
Blackwell Science Publ, Oxford., 1261, 34-41.
https://doi.org/10.1111/j.1749-6632.2012.06623.x

Pilipović I, Radojević K, Perišić M, Leposavić G. Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network. in Neuroimmunomodulation in Health and Disease I. 2012;1261:34-41.
doi:10.1111/j.1749-6632.2012.06623.x .

Pilipović, Ivan, Radojević, Katarina, Perišić, Milica, Leposavić, Gordana, "Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network" in Neuroimmunomodulation in Health and Disease I, 1261 (2012):34-41,
https://doi.org/10.1111/j.1749-6632.2012.06623.x . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Perišić, M.
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1510
AB  - The thymus plays a critical role in establishing and maintaining the peripheral T-cell pool. It does so by providing a microenvironment within which T-cell precursors differentiate and undergo selection processes to create a functional population of major histocompatibility complex-restricted, self-tolerant T cells. These cells are central to adaptive immunity. Thymic T-cell development is influenced by locally produced soluble factors and cell-to-cell interactions, as well as by sympathetic noradrenergic and endocrine system signalling. Thymic lymphoid and non-lymphoid cells have been shown not only to express beta- and alpha(1)-adrenoceptors (ARs), but also to synthesize catecholamines (CAs). Thus, it is suggested that CAs influence T-cell development via both neurocrine/endocrine and autocrine/paracrine action, and that they serve as immunotransmitters between thymocytes and nerves. CAs acting at multiple sites along the thymocyte developmental route affect T-cell generation not only numerically, but also qualitatively. Thymic CA level and synthesis, as well as AR expression exhibit sex steroid-mediated sexual dimorphism. Moreover, the influence of CAs on T-cell development exhibits glucocorticoid-dependent plasticity. This review summarizes recent findings in this field and our current understanding of complex and multifaceted neuroendocrine-immune communications at thymic level.
PB  - Acad Sciences Czech Republic, Inst Physiology, Prague 4
T2  - Physiological Research
T1  - Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity
VL  - 60
IS  - SUPPL.1
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1510
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Perišić, M.",
year = "2011",
abstract = "The thymus plays a critical role in establishing and maintaining the peripheral T-cell pool. It does so by providing a microenvironment within which T-cell precursors differentiate and undergo selection processes to create a functional population of major histocompatibility complex-restricted, self-tolerant T cells. These cells are central to adaptive immunity. Thymic T-cell development is influenced by locally produced soluble factors and cell-to-cell interactions, as well as by sympathetic noradrenergic and endocrine system signalling. Thymic lymphoid and non-lymphoid cells have been shown not only to express beta- and alpha(1)-adrenoceptors (ARs), but also to synthesize catecholamines (CAs). Thus, it is suggested that CAs influence T-cell development via both neurocrine/endocrine and autocrine/paracrine action, and that they serve as immunotransmitters between thymocytes and nerves. CAs acting at multiple sites along the thymocyte developmental route affect T-cell generation not only numerically, but also qualitatively. Thymic CA level and synthesis, as well as AR expression exhibit sex steroid-mediated sexual dimorphism. Moreover, the influence of CAs on T-cell development exhibits glucocorticoid-dependent plasticity. This review summarizes recent findings in this field and our current understanding of complex and multifaceted neuroendocrine-immune communications at thymic level.",
publisher = "Acad Sciences Czech Republic, Inst Physiology, Prague 4",
journal = "Physiological Research",
title = "Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity",
volume = "60",
number = "SUPPL.1",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1510"
}

Leposavić, G., Pilipović, I.,& Perišić, M.. (2011). Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity. in Physiological Research
Acad Sciences Czech Republic, Inst Physiology, Prague 4., 60(SUPPL.1).
https://hdl.handle.net/21.15107/rcub_farfar_1510

Leposavić G, Pilipović I, Perišić M. Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity. in Physiological Research. 2011;60(SUPPL.1).
https://hdl.handle.net/21.15107/rcub_farfar_1510 .

Leposavić, Gordana, Pilipović, Ivan, Perišić, M., "Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity" in Physiological Research, 60, no. SUPPL.1 (2011),
https://hdl.handle.net/21.15107/rcub_farfar_1510 .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Perišić, Milica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1466
AB  - Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naive T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via beta(2)- and alpha(1)-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of beta(2)- and alpha(1)-AR-expressing thymic nonlymphoid cells and the alpha(1)-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving alpha(1)-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naive T cell output. Copyright
PB  - Karger, Basel
T2  - NeuroImmunoModulation
T1  - Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity
VL  - 18
IS  - 5
SP  - 290
EP  - 308
DO  - 10.1159/000329499
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Perišić, Milica",
year = "2011",
abstract = "Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naive T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via beta(2)- and alpha(1)-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of beta(2)- and alpha(1)-AR-expressing thymic nonlymphoid cells and the alpha(1)-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving alpha(1)-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naive T cell output. Copyright",
publisher = "Karger, Basel",
journal = "NeuroImmunoModulation",
title = "Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity",
volume = "18",
number = "5",
pages = "290-308",
doi = "10.1159/000329499"
}

Leposavić, G., Pilipović, I.,& Perišić, M.. (2011). Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity. in NeuroImmunoModulation
Karger, Basel., 18(5), 290-308.
https://doi.org/10.1159/000329499

Leposavić G, Pilipović I, Perišić M. Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity. in NeuroImmunoModulation. 2011;18(5):290-308.
doi:10.1159/000329499 .

Leposavić, Gordana, Pilipović, Ivan, Perišić, Milica, "Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity" in NeuroImmunoModulation, 18, no. 5 (2011):290-308,
https://doi.org/10.1159/000329499 . .

TY  - JOUR
AU  - Perišić, Milica
AU  - Arsenović-Ranin, Nevena
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Pešić, Vesna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1403
AB  - A commonly held view that ovarian hormones are causally involved in age-associated thymic involution has been recently challenged. In particular, their relevance in the progression of thymic involution has been disputed. To reassess this issue 10-month-old rats with well advanced thymic involutive changes were ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development and levels of recent thymic emigrants (RTEs) were examined in peripheral blood and spleen. In addition, the distribution of major conventional and regulatory T-cell subsets was analyzed in the same peripheral lymphocyte compartments. Ovariectomy increased thymic weight and cellularity above the levels in both 10-month-old and age-matched controls indicating that ovarian hormone ablation not only prevented further progression of thymic involution, hut also reversed it. The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of nave T cells as indicated by elevated levels of both CD4 + and CD8 + RTEs in peripheral blood and spleen. The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4 + CD8 + T cell receptor (TCR)alpha beta(low) stage were reduced; the relative numbers of CD4 + CD8 + TCR alpha beta(low) cells entering positive selection and their immediate CD4 + CD8 + TCR alpha beta(high) descendents were increased, while those of the most mature CD4 + CD8 and CD4 CD8 + TCR alpha beta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4 + CD8 + thymocyte subset. The augmented thymic output of naive T cells in Ovx rats most likely reflected an early disinhibition of thymocyte development followed by increased positive/reduced negative selection, at least partly, due to raised thymocyte surface Thy-1 expression. The greater number of CD4 + CD25 + Foxp3 + cells in both thymus and peripheral blood suggested augmented thymic production of these cells. In addition, an increased CD4 + /CD8 + cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone ablation led not only to increased diversity of the T-cell repertoire, but also to a new balance among distinct T-cell subsets in the periphery.
PB  - Elsevier Gmbh, Urban & Fischer Verlag, Jena
T2  - Immunobiology
T1  - Role of ovarian hormones in age-associated thymic involution revisited
VL  - 215
IS  - 4
SP  - 275
EP  - 293
DO  - 10.1016/j.imbio.2009.06.012
ER  - 

@article{
author = "Perišić, Milica and Arsenović-Ranin, Nevena and Pilipović, Ivan and Kosec, Duško and Pešić, Vesna and Radojević, Katarina and Leposavić, Gordana",
year = "2010",
abstract = "A commonly held view that ovarian hormones are causally involved in age-associated thymic involution has been recently challenged. In particular, their relevance in the progression of thymic involution has been disputed. To reassess this issue 10-month-old rats with well advanced thymic involutive changes were ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development and levels of recent thymic emigrants (RTEs) were examined in peripheral blood and spleen. In addition, the distribution of major conventional and regulatory T-cell subsets was analyzed in the same peripheral lymphocyte compartments. Ovariectomy increased thymic weight and cellularity above the levels in both 10-month-old and age-matched controls indicating that ovarian hormone ablation not only prevented further progression of thymic involution, hut also reversed it. The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of nave T cells as indicated by elevated levels of both CD4 + and CD8 + RTEs in peripheral blood and spleen. The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4 + CD8 + T cell receptor (TCR)alpha beta(low) stage were reduced; the relative numbers of CD4 + CD8 + TCR alpha beta(low) cells entering positive selection and their immediate CD4 + CD8 + TCR alpha beta(high) descendents were increased, while those of the most mature CD4 + CD8 and CD4 CD8 + TCR alpha beta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4 + CD8 + thymocyte subset. The augmented thymic output of naive T cells in Ovx rats most likely reflected an early disinhibition of thymocyte development followed by increased positive/reduced negative selection, at least partly, due to raised thymocyte surface Thy-1 expression. The greater number of CD4 + CD25 + Foxp3 + cells in both thymus and peripheral blood suggested augmented thymic production of these cells. In addition, an increased CD4 + /CD8 + cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone ablation led not only to increased diversity of the T-cell repertoire, but also to a new balance among distinct T-cell subsets in the periphery.",
publisher = "Elsevier Gmbh, Urban & Fischer Verlag, Jena",
journal = "Immunobiology",
title = "Role of ovarian hormones in age-associated thymic involution revisited",
volume = "215",
number = "4",
pages = "275-293",
doi = "10.1016/j.imbio.2009.06.012"
}

Perišić, M., Arsenović-Ranin, N., Pilipović, I., Kosec, D., Pešić, V., Radojević, K.,& Leposavić, G.. (2010). Role of ovarian hormones in age-associated thymic involution revisited. in Immunobiology
Elsevier Gmbh, Urban & Fischer Verlag, Jena., 215(4), 275-293.
https://doi.org/10.1016/j.imbio.2009.06.012

Perišić M, Arsenović-Ranin N, Pilipović I, Kosec D, Pešić V, Radojević K, Leposavić G. Role of ovarian hormones in age-associated thymic involution revisited. in Immunobiology. 2010;215(4):275-293.
doi:10.1016/j.imbio.2009.06.012 .

Perišić, Milica, Arsenović-Ranin, Nevena, Pilipović, Ivan, Kosec, Duško, Pešić, Vesna, Radojević, Katarina, Leposavić, Gordana, "Role of ovarian hormones in age-associated thymic involution revisited" in Immunobiology, 215, no. 4 (2010):275-293,
https://doi.org/10.1016/j.imbio.2009.06.012 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Perišić, M.
AU  - Pešić, Vesna
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1381
AB  - There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P  lt  0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P  lt  0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P  lt  0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.
PB  - Assoc Bras Divulg Cientifica, Ribeirao Preto
T2  - Brazilian Journal of Medical and Biological Research
T1  - Glucocorticoids, master modulators of the thymic catecholaminergic system?
VL  - 43
IS  - 3
SP  - 279
EP  - 284
DO  - 10.1590/S0100-879X2010007500005
ER  - 

@article{
author = "Pilipović, Ivan and Kosec, Duško and Radojević, Katarina and Perišić, M. and Pešić, Vesna and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2010",
abstract = "There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P  lt  0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P  lt  0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P  lt  0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.",
publisher = "Assoc Bras Divulg Cientifica, Ribeirao Preto",
journal = "Brazilian Journal of Medical and Biological Research",
title = "Glucocorticoids, master modulators of the thymic catecholaminergic system?",
volume = "43",
number = "3",
pages = "279-284",
doi = "10.1590/S0100-879X2010007500005"
}

Pilipović, I., Kosec, D., Radojević, K., Perišić, M., Pešić, V., Stojić-Vukanić, Z.,& Leposavić, G.. (2010). Glucocorticoids, master modulators of the thymic catecholaminergic system?. in Brazilian Journal of Medical and Biological Research
Assoc Bras Divulg Cientifica, Ribeirao Preto., 43(3), 279-284.
https://doi.org/10.1590/S0100-879X2010007500005

Pilipović I, Kosec D, Radojević K, Perišić M, Pešić V, Stojić-Vukanić Z, Leposavić G. Glucocorticoids, master modulators of the thymic catecholaminergic system?. in Brazilian Journal of Medical and Biological Research. 2010;43(3):279-284.
doi:10.1590/S0100-879X2010007500005 .

Pilipović, Ivan, Kosec, Duško, Radojević, Katarina, Perišić, M., Pešić, Vesna, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Glucocorticoids, master modulators of the thymic catecholaminergic system?" in Brazilian Journal of Medical and Biological Research, 43, no. 3 (2010):279-284,
https://doi.org/10.1590/S0100-879X2010007500005 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pešić, Vesna
AU  - Stojić-Vukanić, Zorica
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Perišić, M.
AU  - Pilipović, Ivan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1358
AB  - Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development
VL  - 45
IS  - 12
SP  - 918
EP  - 935
DO  - 10.1016/j.exger.2010.08.011
ER  - 

@article{
author = "Leposavić, Gordana and Pešić, Vesna and Stojić-Vukanić, Zorica and Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Perišić, M. and Pilipović, Ivan",
year = "2010",
abstract = "Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development",
volume = "45",
number = "12",
pages = "918-935",
doi = "10.1016/j.exger.2010.08.011"
}

Leposavić, G., Pešić, V., Stojić-Vukanić, Z., Radojević, K., Arsenović-Ranin, N., Kosec, D., Perišić, M.,& Pilipović, I.. (2010). Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 45(12), 918-935.
https://doi.org/10.1016/j.exger.2010.08.011

Leposavić G, Pešić V, Stojić-Vukanić Z, Radojević K, Arsenović-Ranin N, Kosec D, Perišić M, Pilipović I. Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology. 2010;45(12):918-935.
doi:10.1016/j.exger.2010.08.011 .

Leposavić, Gordana, Pešić, Vesna, Stojić-Vukanić, Zorica, Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Perišić, M., Pilipović, Ivan, "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development" in Experimental Gerontology, 45, no. 12 (2010):918-935,
https://doi.org/10.1016/j.exger.2010.08.011 . .

TY  - JOUR
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Rakin, Ana
AU  - Leposavić, Gordana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1302
AB  - The present study was undertaken to reassess the recently challenged role of ovarian hormones in age-associated thymic involution. For this purpose, in eleven-month-old peripubertally ovariectomized (Ox) rats we analyzed: i) thymic weight and cellularity, ii) size of CD4+CD8+ double-positive (DP) thymocyte population, which is believed to correlate to the thymic capacity to export mature T cells, iii) number of recent thymic emigrants (RTEs), and iv) number of peripheral blood CD4+ and CD8+ lymphocytes. It was found that both thymic weight and cellularity were greater in Ox than in control rats. In addition, in Ox rats the numbers of DP thymocytes and both CD4+ and CD8+ RTEs, were significantly greater than in controls, indicating a more efficient generation of T cells in these rats. Furthermore, these findings, coupled with data indicating that the number of neither CD4+ nor CD8+ peripheral blood lymphocytes was affected by ovariectomy, most likely, suggest a reduced homeostatic proliferation of memory cells in Ox rats, i.e. broadening of TCR peripheral repertoire without changes in the overall number of T cells leading to a more efficient response to newly encountered antigens. The results indicate that the ovarian steroid deprivation from early peripubertal period leads to a long lasting postponement/alleviation of age-associated decline in T-cell mediated immune response.
AB  - Ova istraživanja su preduzeta sa ciljem da se preispita uloga gonadnih hormona u involuciji timusa, koja je nedavno dovedena u pitanje. U tom cilju je kod 11 meseci starih ženki pacova, koje su ovarijektomisane (Ox) u peripubertetnom uzrastu, analizirana: i) težina i celularnost timusa, ii) broj CD4+CD8+ dvostruko pozitivnih (DP) timocita, za koji se smatra da odražavaju sposobnost organa da generiše zrele T limfocite, iii) broj neposrednih emigranata iz timusa (RTE) i iv) ukupan broj CD4+ i CD8+ limfocita u perifernoj krvi. Dokazano je da su težina i celularnost timusa bile značajno veće u Ox životinja. Kod ovih životinja je nađen i povećan broj DP timocita, kao i CD4+ i CD8+ RTE, što ukazuje na efikasniju produkciju T ćelija u njihovom timusu. Ovaj nalaz, u kontekstu nepromenjenog broja CD4+ i CD8+ ćelija u perifernoj krvi, takođe sugeriše smanjenu homeostatsku proliferaciju memorijskih ćelija, odnosno ukazuje na kvalitativne promene u perifernom T ćelijskom repertoaru (koje obezbeđuju efikasniji odgovor na nove antigene) bez kvantitativnih promena. U celini, rezultati ukazuju da u odsustvu hormona ovarijuma počevši od ranog peripubertetnog uzrasta dolazi do značajnog odlaganja/ublažavanja involucije timusa i posledičnih promena na periferiji.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output
T1  - Peripubertetna ovarijektomija obezbeđuje dugotrajno odlaganje starenjem uslovljenog smanjenja celularnosti timusa i produkcije T limfocita
VL  - 59
IS  - 1
SP  - 3
EP  - 15
DO  - 10.2298/AVB0901003P
ER  - 

@article{
author = "Perišić, Milica and Kosec, Duško and Pilipović, Ivan and Radojević, Katarina and Pešić, Vesna and Rakin, Ana and Leposavić, Gordana",
year = "2009",
abstract = "The present study was undertaken to reassess the recently challenged role of ovarian hormones in age-associated thymic involution. For this purpose, in eleven-month-old peripubertally ovariectomized (Ox) rats we analyzed: i) thymic weight and cellularity, ii) size of CD4+CD8+ double-positive (DP) thymocyte population, which is believed to correlate to the thymic capacity to export mature T cells, iii) number of recent thymic emigrants (RTEs), and iv) number of peripheral blood CD4+ and CD8+ lymphocytes. It was found that both thymic weight and cellularity were greater in Ox than in control rats. In addition, in Ox rats the numbers of DP thymocytes and both CD4+ and CD8+ RTEs, were significantly greater than in controls, indicating a more efficient generation of T cells in these rats. Furthermore, these findings, coupled with data indicating that the number of neither CD4+ nor CD8+ peripheral blood lymphocytes was affected by ovariectomy, most likely, suggest a reduced homeostatic proliferation of memory cells in Ox rats, i.e. broadening of TCR peripheral repertoire without changes in the overall number of T cells leading to a more efficient response to newly encountered antigens. The results indicate that the ovarian steroid deprivation from early peripubertal period leads to a long lasting postponement/alleviation of age-associated decline in T-cell mediated immune response., Ova istraživanja su preduzeta sa ciljem da se preispita uloga gonadnih hormona u involuciji timusa, koja je nedavno dovedena u pitanje. U tom cilju je kod 11 meseci starih ženki pacova, koje su ovarijektomisane (Ox) u peripubertetnom uzrastu, analizirana: i) težina i celularnost timusa, ii) broj CD4+CD8+ dvostruko pozitivnih (DP) timocita, za koji se smatra da odražavaju sposobnost organa da generiše zrele T limfocite, iii) broj neposrednih emigranata iz timusa (RTE) i iv) ukupan broj CD4+ i CD8+ limfocita u perifernoj krvi. Dokazano je da su težina i celularnost timusa bile značajno veće u Ox životinja. Kod ovih životinja je nađen i povećan broj DP timocita, kao i CD4+ i CD8+ RTE, što ukazuje na efikasniju produkciju T ćelija u njihovom timusu. Ovaj nalaz, u kontekstu nepromenjenog broja CD4+ i CD8+ ćelija u perifernoj krvi, takođe sugeriše smanjenu homeostatsku proliferaciju memorijskih ćelija, odnosno ukazuje na kvalitativne promene u perifernom T ćelijskom repertoaru (koje obezbeđuju efikasniji odgovor na nove antigene) bez kvantitativnih promena. U celini, rezultati ukazuju da u odsustvu hormona ovarijuma počevši od ranog peripubertetnog uzrasta dolazi do značajnog odlaganja/ublažavanja involucije timusa i posledičnih promena na periferiji.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output, Peripubertetna ovarijektomija obezbeđuje dugotrajno odlaganje starenjem uslovljenog smanjenja celularnosti timusa i produkcije T limfocita",
volume = "59",
number = "1",
pages = "3-15",
doi = "10.2298/AVB0901003P"
}

Perišić, M., Kosec, D., Pilipović, I., Radojević, K., Pešić, V., Rakin, A.,& Leposavić, G.. (2009). Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 59(1), 3-15.
https://doi.org/10.2298/AVB0901003P

Perišić M, Kosec D, Pilipović I, Radojević K, Pešić V, Rakin A, Leposavić G. Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output. in Acta veterinaria. 2009;59(1):3-15.
doi:10.2298/AVB0901003P .

Perišić, Milica, Kosec, Duško, Pilipović, Ivan, Radojević, Katarina, Pešić, Vesna, Rakin, Ana, Leposavić, Gordana, "Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output" in Acta veterinaria, 59, no. 1 (2009):3-15,
https://doi.org/10.2298/AVB0901003P . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Pilipović, Ivan
AU  - Stanojević, Stanislava
AU  - Mitić, Katarina
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Leposavić, Gordana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1278
AB  - Using both immunocytochemical and flow cytometric analyses of rat peritoneal exudate cells constitutive expression of tyrosine hydroxylase and both beta(2)- and alpha(1)-adrenoceptors on macrophages was revealed. Furthermore, according to the characteristic assemblage of tyrosine hydroxylase and adrenoceptor subtype expression different macrophage subsets were identified. In vitro treatment of macrophages with the nonselective alpha,beta-adrenoceptor agonist arterenol and/or the beta-adrenoceptor antagonist propranolol indicated that beta-adrenoceptors potentiated nitric oxide (NO) production and suggested alpha-adrenoceptor-mediated suppression of hydrogen peroxide (H2O2) production. An increase in H2O2 production in the presence of the alpha(1)-adrenoceptor antagonist ebrantil provided support for this. Chronic propranolol treatment in vivo led to increased NO and H2O2 production by peritoneal macrophages. Furthermore, this treatment resulted in opposing effects on the expression Of beta(2)- and alpha(1)-adrenoceptors on peritoneal macrophages (a stimulatory effect on beta(2)-adrenoceptors and a suppressive effect on alpha(1)-adrenoceptors). In conclusion, a subset of resident peritoneal macrophages synthesizes catecholamines, which may exert differential effects on H2O2 and NO production via distinct adrenoceptors. Finally, chronic propranolol treatment affected adrenoceptor expression on peritoneal macrophages and altered their capacity to generate NO and H2O2.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide
VL  - 211
IS  - 1-2
SP  - 56
EP  - 65
DO  - 10.1016/j.jneuroim.2009.03.014
ER  - 

@article{
author = "Dimitrijević, Mirjana and Pilipović, Ivan and Stanojević, Stanislava and Mitić, Katarina and Radojević, Katarina and Pešić, Vesna and Leposavić, Gordana",
year = "2009",
abstract = "Using both immunocytochemical and flow cytometric analyses of rat peritoneal exudate cells constitutive expression of tyrosine hydroxylase and both beta(2)- and alpha(1)-adrenoceptors on macrophages was revealed. Furthermore, according to the characteristic assemblage of tyrosine hydroxylase and adrenoceptor subtype expression different macrophage subsets were identified. In vitro treatment of macrophages with the nonselective alpha,beta-adrenoceptor agonist arterenol and/or the beta-adrenoceptor antagonist propranolol indicated that beta-adrenoceptors potentiated nitric oxide (NO) production and suggested alpha-adrenoceptor-mediated suppression of hydrogen peroxide (H2O2) production. An increase in H2O2 production in the presence of the alpha(1)-adrenoceptor antagonist ebrantil provided support for this. Chronic propranolol treatment in vivo led to increased NO and H2O2 production by peritoneal macrophages. Furthermore, this treatment resulted in opposing effects on the expression Of beta(2)- and alpha(1)-adrenoceptors on peritoneal macrophages (a stimulatory effect on beta(2)-adrenoceptors and a suppressive effect on alpha(1)-adrenoceptors). In conclusion, a subset of resident peritoneal macrophages synthesizes catecholamines, which may exert differential effects on H2O2 and NO production via distinct adrenoceptors. Finally, chronic propranolol treatment affected adrenoceptor expression on peritoneal macrophages and altered their capacity to generate NO and H2O2.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide",
volume = "211",
number = "1-2",
pages = "56-65",
doi = "10.1016/j.jneuroim.2009.03.014"
}

Dimitrijević, M., Pilipović, I., Stanojević, S., Mitić, K., Radojević, K., Pešić, V.,& Leposavić, G.. (2009). Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 211(1-2), 56-65.
https://doi.org/10.1016/j.jneuroim.2009.03.014

Dimitrijević M, Pilipović I, Stanojević S, Mitić K, Radojević K, Pešić V, Leposavić G. Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide. in Journal of Neuroimmunology. 2009;211(1-2):56-65.
doi:10.1016/j.jneuroim.2009.03.014 .

Dimitrijević, Mirjana, Pilipović, Ivan, Stanojević, Stanislava, Mitić, Katarina, Radojević, Katarina, Pešić, Vesna, Leposavić, Gordana, "Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide" in Journal of Neuroimmunology, 211, no. 1-2 (2009):56-65,
https://doi.org/10.1016/j.jneuroim.2009.03.014 . .

TY  - JOUR
AU  - Pešić, Vesna
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Perišić, M.
AU  - Vidić-Danković, Biljana
AU  - Leposavić, Gordana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1179
AB  - The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCR alpha beta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCR alpha beta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCR alpha beta(high) high thymocytes. In urapidil-administered rats the percentage of CD4+CD8-SP TCR alpha beta(high) thymocytes was increased, while that of the CD4-CD8+ TCR alpha beta(high) was reduced. compared with controls. In addition, proportions of CD4+CD25+ RT6.1- and CD161+TCR alpha beta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis
VL  - 214
IS  - 1-2
SP  - 55
EP  - 66
DO  - 10.1016/j.jneuroim.2009.06.018
ER  - 

@article{
author = "Pešić, Vesna and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Perišić, M. and Vidić-Danković, Biljana and Leposavić, Gordana",
year = "2009",
abstract = "The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCR alpha beta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCR alpha beta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCR alpha beta(high) high thymocytes. In urapidil-administered rats the percentage of CD4+CD8-SP TCR alpha beta(high) thymocytes was increased, while that of the CD4-CD8+ TCR alpha beta(high) was reduced. compared with controls. In addition, proportions of CD4+CD25+ RT6.1- and CD161+TCR alpha beta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis",
volume = "214",
number = "1-2",
pages = "55-66",
doi = "10.1016/j.jneuroim.2009.06.018"
}

Pešić, V., Kosec, D., Radojević, K., Pilipović, I., Perišić, M., Vidić-Danković, B.,& Leposavić, G.. (2009). Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 214(1-2), 55-66.
https://doi.org/10.1016/j.jneuroim.2009.06.018

Pešić V, Kosec D, Radojević K, Pilipović I, Perišić M, Vidić-Danković B, Leposavić G. Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis. in Journal of Neuroimmunology. 2009;214(1-2):55-66.
doi:10.1016/j.jneuroim.2009.06.018 .

Pešić, Vesna, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Perišić, M., Vidić-Danković, Biljana, Leposavić, Gordana, "Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis" in Journal of Neuroimmunology, 214, no. 1-2 (2009):55-66,
https://doi.org/10.1016/j.jneuroim.2009.06.018 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Arsenović-Ranin, Nevena
AU  - Radojević, Katarina
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1245
AB  - Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats
VL  - 23
IS  - 2
SP  - 294
EP  - 304
DO  - 10.1016/j.bbi.2008.11.002
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica and Kosec, Duško and Arsenović-Ranin, Nevena and Radojević, Katarina and Stojić-Vukanić, Zorica and Pilipović, Ivan",
year = "2009",
abstract = "Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats",
volume = "23",
number = "2",
pages = "294-304",
doi = "10.1016/j.bbi.2008.11.002"
}

Leposavić, G., Perišić, M., Kosec, D., Arsenović-Ranin, N., Radojević, K., Stojić-Vukanić, Z.,& Pilipović, I.. (2009). Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 23(2), 294-304.
https://doi.org/10.1016/j.bbi.2008.11.002

Leposavić G, Perišić M, Kosec D, Arsenović-Ranin N, Radojević K, Stojić-Vukanić Z, Pilipović I. Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity. 2009;23(2):294-304.
doi:10.1016/j.bbi.2008.11.002 .

Leposavić, Gordana, Perišić, Milica, Kosec, Duško, Arsenović-Ranin, Nevena, Radojević, Katarina, Stojić-Vukanić, Zorica, Pilipović, Ivan, "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats" in Brain Behavior and Immunity, 23, no. 2 (2009):294-304,
https://doi.org/10.1016/j.bbi.2008.11.002 . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Rauski, Aleksandra
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1197
AB  - A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009
PB  - Royal Soc Medicine Press Ltd, London
T2  - Experimental Biology and Medicine
T1  - Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats
VL  - 234
IS  - 9
SP  - 1067
EP  - 1074
DO  - 10.3181/0902-RM-63
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Rauski, Aleksandra and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Leposavić, Gordana",
year = "2009",
abstract = "A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009",
publisher = "Royal Soc Medicine Press Ltd, London",
journal = "Experimental Biology and Medicine",
title = "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats",
volume = "234",
number = "9",
pages = "1067-1074",
doi = "10.3181/0902-RM-63"
}

Stojić-Vukanić, Z., Rauski, A., Kosec, D., Radojević, K., Pilipović, I.,& Leposavić, G.. (2009). Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine
Royal Soc Medicine Press Ltd, London., 234(9), 1067-1074.
https://doi.org/10.3181/0902-RM-63

Stojić-Vukanić Z, Rauski A, Kosec D, Radojević K, Pilipović I, Leposavić G. Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine. 2009;234(9):1067-1074.
doi:10.3181/0902-RM-63 .

Stojić-Vukanić, Zorica, Rauski, Aleksandra, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Leposavić, Gordana, "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats" in Experimental Biology and Medicine, 234, no. 9 (2009):1067-1074,
https://doi.org/10.3181/0902-RM-63 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Perišić, Milica
AU  - Kosec, Duško
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1094
AB  - In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated tit response to antigen. In establishing and maintaining the peripheral T-cell pool, the thymus plays a critical role. It does so by providing a microenvironment within which T cell precursors proliferate, differentiate and Undergo selection processes to create a fully functional population of major histocompatibility complex restricted, self-tolerant T cells. The control of the thymic function involves intrathymic, as well as sympathetic nervous and endocrine system signalling. In addition to postganglionic noradrenergic fibres, both thymic lymphoid and non-lymphoid cells, including epithelial cells and macrophages. have been demo nstrated to express tyrosine hydroxylase (TH), and Suggested to form a local non-neural catecholaminergic cell network. A higher level of noradrenaline has been found in male than in female rat thymi. and a role of,gonadal hormones ill providing this dimorphism has been demonstrated. In addition, thymic lymphoid and non-lymphoid cells, including those expressing TH, have been found to bear beta- and alpha(1)-adrenoceptors (ARs) and a role of gonadal hormones in regulation of, at least. beta-AR density and signalling has been Suggested. These findings have also entailed conclusion that catecholamiens (CAs) influence T-cell development, not only via neurocrine/endocrine, but also via autocrine/paracrine action. Generally, CAs have been shown to exert an inhibitory influence on thymopoiesis. Role of alpha(1)- and beta-R-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the Manuscript.
PB  - Elsevier Science BV, Amsterdam
T2  - Autonomic Neuroscience-Basic & Clinical
T1  - Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development
VL  - 144
IS  - 1-2
SP  - 1
EP  - 12
DO  - 10.1016/j.autneu.2008.09.003
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Radojević, Katarina and Pešić, Vesna and Perišić, Milica and Kosec, Duško",
year = "2008",
abstract = "In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated tit response to antigen. In establishing and maintaining the peripheral T-cell pool, the thymus plays a critical role. It does so by providing a microenvironment within which T cell precursors proliferate, differentiate and Undergo selection processes to create a fully functional population of major histocompatibility complex restricted, self-tolerant T cells. The control of the thymic function involves intrathymic, as well as sympathetic nervous and endocrine system signalling. In addition to postganglionic noradrenergic fibres, both thymic lymphoid and non-lymphoid cells, including epithelial cells and macrophages. have been demo nstrated to express tyrosine hydroxylase (TH), and Suggested to form a local non-neural catecholaminergic cell network. A higher level of noradrenaline has been found in male than in female rat thymi. and a role of,gonadal hormones ill providing this dimorphism has been demonstrated. In addition, thymic lymphoid and non-lymphoid cells, including those expressing TH, have been found to bear beta- and alpha(1)-adrenoceptors (ARs) and a role of gonadal hormones in regulation of, at least. beta-AR density and signalling has been Suggested. These findings have also entailed conclusion that catecholamiens (CAs) influence T-cell development, not only via neurocrine/endocrine, but also via autocrine/paracrine action. Generally, CAs have been shown to exert an inhibitory influence on thymopoiesis. Role of alpha(1)- and beta-R-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the Manuscript.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Autonomic Neuroscience-Basic & Clinical",
title = "Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development",
volume = "144",
number = "1-2",
pages = "1-12",
doi = "10.1016/j.autneu.2008.09.003"
}

Leposavić, G., Pilipović, I., Radojević, K., Pešić, V., Perišić, M.,& Kosec, D.. (2008). Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development. in Autonomic Neuroscience-Basic & Clinical
Elsevier Science BV, Amsterdam., 144(1-2), 1-12.
https://doi.org/10.1016/j.autneu.2008.09.003

Leposavić G, Pilipović I, Radojević K, Pešić V, Perišić M, Kosec D. Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development. in Autonomic Neuroscience-Basic & Clinical. 2008;144(1-2):1-12.
doi:10.1016/j.autneu.2008.09.003 .

Leposavić, Gordana, Pilipović, Ivan, Radojević, Katarina, Pešić, Vesna, Perišić, Milica, Kosec, Duško, "Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development" in Autonomic Neuroscience-Basic & Clinical, 144, no. 1-2 (2008):1-12,
https://doi.org/10.1016/j.autneu.2008.09.003 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vidić-Danković, Biljana
AU  - Perišić, Milica
AU  - Radojević, Katarina
AU  - Čolić, Miodrag
AU  - Todorović, Vera
AU  - Leposavić, Gordana
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1080
AB  - The study was undertaken to explore whether there were: i) apart from neural and circulatory, some other sources of catecholamines (CAs) in rat thymus and ii) gender-specific differences in thymic CA levels, and if so to elucidate the role of sex steroids in this phenomenon. Tyrosine hydroxylase (TH) immunoreactivity was found in thymocytes and thymic epithelial cells (some of which showed morphological features of nurse cells). The density of CA-synthesizing cells was greater in male than in female rats. Noradrenaline (NA), but not dopamine (DA), was detected in thymocytes. NA and DA levels in thymi, and the NA level in thymocytes, were higher in male rats. To explore the Putative role of sex steroids in this dichotomy in the thymi of adult rats gonadectomized (Gx) or sham-Gx at the age of 30 days the density of TH+ cells and CA levels were measured. Gonadectomy abolished sexual dimorphism in the density of thymic TH+ cells (diminishing their density in male rats) and thymic CA levels (the NA levels were reduced in rats of both sexes and also the DA level in male rats). Therefore, it can be assumed that testicular and ovarian hormones control thymic NA and DA levels via different mechanisms. Moreover, in Gx rats, despite the decrease in the overall thymic NA level, an increase in the thymocyte NA level was found indicating that gonadal hormones exert differential effects on the NA level in distinct thymic cellular compartments.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones
VL  - 195
IS  - 1-2
SP  - 7
EP  - 20
DO  - 10.1016/j.jneuroim.2007.12.006
ER  - 

@article{
author = "Pilipović, Ivan and Vidić-Danković, Biljana and Perišić, Milica and Radojević, Katarina and Čolić, Miodrag and Todorović, Vera and Leposavić, Gordana",
year = "2008",
abstract = "The study was undertaken to explore whether there were: i) apart from neural and circulatory, some other sources of catecholamines (CAs) in rat thymus and ii) gender-specific differences in thymic CA levels, and if so to elucidate the role of sex steroids in this phenomenon. Tyrosine hydroxylase (TH) immunoreactivity was found in thymocytes and thymic epithelial cells (some of which showed morphological features of nurse cells). The density of CA-synthesizing cells was greater in male than in female rats. Noradrenaline (NA), but not dopamine (DA), was detected in thymocytes. NA and DA levels in thymi, and the NA level in thymocytes, were higher in male rats. To explore the Putative role of sex steroids in this dichotomy in the thymi of adult rats gonadectomized (Gx) or sham-Gx at the age of 30 days the density of TH+ cells and CA levels were measured. Gonadectomy abolished sexual dimorphism in the density of thymic TH+ cells (diminishing their density in male rats) and thymic CA levels (the NA levels were reduced in rats of both sexes and also the DA level in male rats). Therefore, it can be assumed that testicular and ovarian hormones control thymic NA and DA levels via different mechanisms. Moreover, in Gx rats, despite the decrease in the overall thymic NA level, an increase in the thymocyte NA level was found indicating that gonadal hormones exert differential effects on the NA level in distinct thymic cellular compartments.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones",
volume = "195",
number = "1-2",
pages = "7-20",
doi = "10.1016/j.jneuroim.2007.12.006"
}

Pilipović, I., Vidić-Danković, B., Perišić, M., Radojević, K., Čolić, M., Todorović, V.,& Leposavić, G.. (2008). Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 195(1-2), 7-20.
https://doi.org/10.1016/j.jneuroim.2007.12.006

Pilipović I, Vidić-Danković B, Perišić M, Radojević K, Čolić M, Todorović V, Leposavić G. Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones. in Journal of Neuroimmunology. 2008;195(1-2):7-20.
doi:10.1016/j.jneuroim.2007.12.006 .

Pilipović, Ivan, Vidić-Danković, Biljana, Perišić, Milica, Radojević, Katarina, Čolić, Miodrag, Todorović, Vera, Leposavić, Gordana, "Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones" in Journal of Neuroimmunology, 195, no. 1-2 (2008):7-20,
https://doi.org/10.1016/j.jneuroim.2007.12.006 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1051
AB  - The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered. Copyright
PB  - Karger, Basel
T2  - NeuroImmunoModulation
T1  - Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines
VL  - 15
IS  - 4-6
SP  - 290
EP  - 322
DO  - 10.1159/000156473
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica",
year = "2008",
abstract = "The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered. Copyright",
publisher = "Karger, Basel",
journal = "NeuroImmunoModulation",
title = "Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines",
volume = "15",
number = "4-6",
pages = "290-322",
doi = "10.1159/000156473"
}

Leposavić, G.,& Perišić, M.. (2008). Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines. in NeuroImmunoModulation
Karger, Basel., 15(4-6), 290-322.
https://doi.org/10.1159/000156473

Leposavić G, Perišić M. Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines. in NeuroImmunoModulation. 2008;15(4-6):290-322.
doi:10.1159/000156473 .

Leposavić, Gordana, Perišić, Milica, "Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines" in NeuroImmunoModulation, 15, no. 4-6 (2008):290-322,
https://doi.org/10.1159/000156473 . .

TY  - JOUR
AU  - Pešić, V.
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Plećaš-Solarović, Bosiljka
AU  - Perišić, M.
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/987
AB  - The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.
PB  - Assoc Bras Divulg Cientifica, Sao Paulo
T2  - Brazilian Journal of Medical and Biological Research
T1  - Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats
VL  - 40
IS  - 11
SP  - 1481
EP  - 1493
DO  - 10.1590/S0100-879X2006005000172
ER  - 

@article{
author = "Pešić, V. and Radojević, Katarina and Kosec, Duško and Plećaš-Solarović, Bosiljka and Perišić, M. and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.",
publisher = "Assoc Bras Divulg Cientifica, Sao Paulo",
journal = "Brazilian Journal of Medical and Biological Research",
title = "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats",
volume = "40",
number = "11",
pages = "1481-1493",
doi = "10.1590/S0100-879X2006005000172"
}

Pešić, V., Radojević, K., Kosec, D., Plećaš-Solarović, B., Perišić, M., Pilipović, I.,& Leposavić, G.. (2007). Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research
Assoc Bras Divulg Cientifica, Sao Paulo., 40(11), 1481-1493.
https://doi.org/10.1590/S0100-879X2006005000172

Pešić V, Radojević K, Kosec D, Plećaš-Solarović B, Perišić M, Pilipović I, Leposavić G. Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research. 2007;40(11):1481-1493.
doi:10.1590/S0100-879X2006005000172 .

Pešić, V., Radojević, Katarina, Kosec, Duško, Plećaš-Solarović, Bosiljka, Perišić, M., Pilipović, Ivan, Leposavić, Gordana, "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats" in Brazilian Journal of Medical and Biological Research, 40, no. 11 (2007):1481-1493,
https://doi.org/10.1590/S0100-879X2006005000172 . .

TY  - JOUR
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pešić, V.
AU  - Pilipović, Ivan
AU  - Perišić, M.
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/957
AB  - To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.
PB  - Bioscientifica Ltd, Bristol
T2  - Journal of Endocrinology
T1  - Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level
VL  - 192
IS  - 3
SP  - 669
EP  - 682
DO  - 10.1677/joe.1.07019
ER  - 

@article{
author = "Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Pešić, V. and Pilipović, Ivan and Perišić, M. and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2007",
abstract = "To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.",
publisher = "Bioscientifica Ltd, Bristol",
journal = "Journal of Endocrinology",
title = "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level",
volume = "192",
number = "3",
pages = "669-682",
doi = "10.1677/joe.1.07019"
}

Radojević, K., Arsenović-Ranin, N., Kosec, D., Pešić, V., Pilipović, I., Perišić, M., Plećaš-Solarović, B.,& Leposavić, G.. (2007). Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology
Bioscientifica Ltd, Bristol., 192(3), 669-682.
https://doi.org/10.1677/joe.1.07019

Radojević K, Arsenović-Ranin N, Kosec D, Pešić V, Pilipović I, Perišić M, Plećaš-Solarović B, Leposavić G. Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology. 2007;192(3):669-682.
doi:10.1677/joe.1.07019 .

Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Pešić, V., Pilipović, Ivan, Perišić, M., Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level" in Journal of Endocrinology, 192, no. 3 (2007):669-682,
https://doi.org/10.1677/joe.1.07019 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Radojević, Katarina
AU  - Vidić-Danković, Biljana
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Perišić, Milica
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/945
AB  - The interactions among the nervous, endocrine and immune system were studied by examining: i) thymic and thymocyte catecholamine levels in adult rats castrated (Cx) at postnatal day 3 and ii) effects of 14-day-long propranolol (P) treatment on main thymocyte differentiational molecule expression in adult non-Cx and Cx rat. The results demonstrated that castration in early postnatal period lowers levels of both neurally- and thymocyte-derived noradrenaline in adult rats, and thereby diminishes beta-adrenoceptor-mediated fine tuning of the T-cell differentiation/maturation. In non-Cx rats P affected TCR alpha beta-dependent stages of thymocyte differentiation/maturation decreasing frequency of CD4+8+ double positive (DP) TCR alpha beta(low) low cells entering selection processes and increasing relative number of positively selected DP TCR alpha beta(high) (most likely due to an increased thymocyte surface density of Thy-1 that is involved in negative control of TCR alpha beta-mediated signaling/selection thresholds) and the most mature CD4+8- TCR alpha beta(high) cells (including CD4+25+ regulatory cells). However, in Cx rats P failed to produce any significant changes in thymocyte subset composition.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats
VL  - 182
IS  - 1-2
SP  - 100
EP  - 115
DO  - 10.1016/j.jneuroim.2006.10.004
ER  - 

@article{
author = "Leposavić, Gordana and Radojević, Katarina and Vidić-Danković, Biljana and Kosec, Duško and Pilipović, Ivan and Perišić, Milica",
year = "2007",
abstract = "The interactions among the nervous, endocrine and immune system were studied by examining: i) thymic and thymocyte catecholamine levels in adult rats castrated (Cx) at postnatal day 3 and ii) effects of 14-day-long propranolol (P) treatment on main thymocyte differentiational molecule expression in adult non-Cx and Cx rat. The results demonstrated that castration in early postnatal period lowers levels of both neurally- and thymocyte-derived noradrenaline in adult rats, and thereby diminishes beta-adrenoceptor-mediated fine tuning of the T-cell differentiation/maturation. In non-Cx rats P affected TCR alpha beta-dependent stages of thymocyte differentiation/maturation decreasing frequency of CD4+8+ double positive (DP) TCR alpha beta(low) low cells entering selection processes and increasing relative number of positively selected DP TCR alpha beta(high) (most likely due to an increased thymocyte surface density of Thy-1 that is involved in negative control of TCR alpha beta-mediated signaling/selection thresholds) and the most mature CD4+8- TCR alpha beta(high) cells (including CD4+25+ regulatory cells). However, in Cx rats P failed to produce any significant changes in thymocyte subset composition.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats",
volume = "182",
number = "1-2",
pages = "100-115",
doi = "10.1016/j.jneuroim.2006.10.004"
}

Leposavić, G., Radojević, K., Vidić-Danković, B., Kosec, D., Pilipović, I.,& Perišić, M.. (2007). Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 182(1-2), 100-115.
https://doi.org/10.1016/j.jneuroim.2006.10.004

Leposavić G, Radojević K, Vidić-Danković B, Kosec D, Pilipović I, Perišić M. Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats. in Journal of Neuroimmunology. 2007;182(1-2):100-115.
doi:10.1016/j.jneuroim.2006.10.004 .

Leposavić, Gordana, Radojević, Katarina, Vidić-Danković, Biljana, Kosec, Duško, Pilipović, Ivan, Perišić, Milica, "Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats" in Journal of Neuroimmunology, 182, no. 1-2 (2007):100-115,
https://doi.org/10.1016/j.jneuroim.2006.10.004 . .

TY  - JOUR
AU  - Pešić, V.
AU  - Plećaš-Solarović, Bosiljka
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Perišić, M.
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/916
AB  - Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.
PB  - Elsevier Science BV, Amsterdam
T2  - International Immunopharmacology
T1  - Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats
VL  - 7
IS  - 5
SP  - 674
EP  - 686
DO  - 10.1016/j.intimp.2007.01.017
ER  - 

@article{
author = "Pešić, V. and Plećaš-Solarović, Bosiljka and Radojević, Katarina and Kosec, Duško and Pilipović, Ivan and Perišić, M. and Leposavić, Gordana",
year = "2007",
abstract = "Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Immunopharmacology",
title = "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats",
volume = "7",
number = "5",
pages = "674-686",
doi = "10.1016/j.intimp.2007.01.017"
}

Pešić, V., Plećaš-Solarović, B., Radojević, K., Kosec, D., Pilipović, I., Perišić, M.,& Leposavić, G.. (2007). Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology
Elsevier Science BV, Amsterdam., 7(5), 674-686.
https://doi.org/10.1016/j.intimp.2007.01.017

Pešić V, Plećaš-Solarović B, Radojević K, Kosec D, Pilipović I, Perišić M, Leposavić G. Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology. 2007;7(5):674-686.
doi:10.1016/j.intimp.2007.01.017 .

Pešić, V., Plećaš-Solarović, Bosiljka, Radojević, Katarina, Kosec, Duško, Pilipović, Ivan, Perišić, M., Leposavić, Gordana, "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats" in International Immunopharmacology, 7, no. 5 (2007):674-686,
https://doi.org/10.1016/j.intimp.2007.01.017 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Rauski, Aleksandra
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Stanojević, S.
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/893
AB  - As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats
VL  - 577
IS  - 1-3
SP  - 170
EP  - 182
DO  - 10.1016/j.ejphar.2007.08.021
ER  - 

@article{
author = "Dimitrijević, Mirjana and Rauski, Aleksandra and Radojević, Katarina and Kosec, Duško and Stanojević, S. and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats",
volume = "577",
number = "1-3",
pages = "170-182",
doi = "10.1016/j.ejphar.2007.08.021"
}

Dimitrijević, M., Rauski, A., Radojević, K., Kosec, D., Stanojević, S., Pilipović, I.,& Leposavić, G.. (2007). beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 577(1-3), 170-182.
https://doi.org/10.1016/j.ejphar.2007.08.021

Dimitrijević M, Rauski A, Radojević K, Kosec D, Stanojević S, Pilipović I, Leposavić G. beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology. 2007;577(1-3):170-182.
doi:10.1016/j.ejphar.2007.08.021 .

Dimitrijević, Mirjana, Rauski, Aleksandra, Radojević, Katarina, Kosec, Duško, Stanojević, S., Pilipović, Ivan, Leposavić, Gordana, "beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats" in European Journal of Pharmacology, 577, no. 1-3 (2007):170-182,
https://doi.org/10.1016/j.ejphar.2007.08.021 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pešić, Vesna
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Plećaš-Solarović, Bosiljka
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/816
AB  - To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCR alpha beta and (ii) Thy-1, which is supposed to be a regulator of TCR alpha beta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCR alpha beta signalling in the development of CD4+25+T-reg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRao-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCR alpha beta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCR alpha beta(high) to the SP TCR alpha beta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T-reg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats
VL  - 41
IS  - 6
SP  - 574
EP  - 589
DO  - 10.1016/j.exger.2006.03.006
ER  - 

@article{
author = "Leposavić, Gordana and Pešić, Vesna and Kosec, Duško and Radojević, Katarina and Arsenović-Ranin, Nevena and Pilipović, Ivan and Perišić, Milica and Plećaš-Solarović, Bosiljka",
year = "2006",
abstract = "To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCR alpha beta and (ii) Thy-1, which is supposed to be a regulator of TCR alpha beta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCR alpha beta signalling in the development of CD4+25+T-reg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRao-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCR alpha beta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCR alpha beta(high) to the SP TCR alpha beta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T-reg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats",
volume = "41",
number = "6",
pages = "574-589",
doi = "10.1016/j.exger.2006.03.006"
}

Leposavić, G., Pešić, V., Kosec, D., Radojević, K., Arsenović-Ranin, N., Pilipović, I., Perišić, M.,& Plećaš-Solarović, B.. (2006). Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 41(6), 574-589.
https://doi.org/10.1016/j.exger.2006.03.006

Leposavić G, Pešić V, Kosec D, Radojević K, Arsenović-Ranin N, Pilipović I, Perišić M, Plećaš-Solarović B. Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats. in Experimental Gerontology. 2006;41(6):574-589.
doi:10.1016/j.exger.2006.03.006 .

Leposavić, Gordana, Pešić, Vesna, Kosec, Duško, Radojević, Katarina, Arsenović-Ranin, Nevena, Pilipović, Ivan, Perišić, Milica, Plećaš-Solarović, Bosiljka, "Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats" in Experimental Gerontology, 41, no. 6 (2006):574-589,
https://doi.org/10.1016/j.exger.2006.03.006 . .