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Role of ovarian hormones in age-associated thymic involution revisited

Authorized Users Only
2010
Authors
Perišić, Milica
Arsenović-Ranin, Nevena
Pilipović, Ivan
Kosec, Duško
Pešić, Vesna
Radojević, Katarina
Leposavić, Gordana
Article (Published version)
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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 outp...ut 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.

Keywords:
Ovarian hormones / Recent thymic emigrants / Thymic involution / Thymopoiesis / T regulatory cells
Source:
Immunobiology, 2010, 215, 4, 275-293
Publisher:
  • Elsevier Gmbh, Urban & Fischer Verlag, Jena
Funding / projects:
  • Neuroendokrina modulacija imunskog odgovora: uloga simpato-adrenomedularnog sistema (RS-145049)

DOI: 10.1016/j.imbio.2009.06.012

ISSN: 0171-2985

PubMed: 19577818

WoS: 000276612400003

Scopus: 2-s2.0-77649234731
[ Google Scholar ]
18
17
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1403
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
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 . .

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