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dc.creatorĐikić, Jasmina
dc.creatorNacka-Aleksić, Mirjana
dc.creatorPilipović, Ivan
dc.creatorStojić-Vukanić, Zorica
dc.creatorBufan, Biljana
dc.creatorKosec, Duško
dc.creatorDimitrijević, Mirjana
dc.creatorLeposavić, Gordana
dc.date.accessioned2019-09-02T11:40:02Z
dc.date.available2019-09-02T11:40:02Z
dc.date.issued2014
dc.identifier.issn0531-5565
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2139
dc.description.abstractAging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCR alpha beta+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naive CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory properties. Compared with young rats, following short-term PMA and ionomycin stimulation in vitro, the frequency of IL-17+ and IFN-gamma+CD4+ T lymphocytes among the spinal cord mononuclear cells from aged rats and the cytokine expression density on a per lymphocyte basis were reduced. Additionally, the increase in the proportion of autoregulatory IL-17+IL-10+ cells on the account of proinflammatory IL-17+IFN-gamma+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity in aged rats. This most likely reflected alterations in the aged rat spinal cord cytokine milieu, which were mirrored in a diminished expression of IL-1 beta mRNA followed by an enhanced expression of IL-6 and TGF-beta mRNA. Overall, the study points to age-related changes in T lymphocytes and other cells from the spinal cord infiltrate which could contribute to the decreased susceptibility of aged rats to the induction of EAE.en
dc.publisherPergamon-Elsevier Science Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsrestrictedAccess
dc.sourceExperimental Gerontology
dc.subjectRaten
dc.subjectAgingen
dc.subjectEAEen
dc.subjectCD134en
dc.subjectIL-17+IL-10+lymphocytesen
dc.titleAge-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitisen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПилиповић, Иван; Димитријевић, Мирјана; Косец, Душко; Стојић-Вуканић, Зорица; Ђикић, Јасмина; Буфан, Биљана; Нацка-Aлексић, Мирјана; Лепосавић, Гордана;
dc.citation.volume58
dc.citation.spage179
dc.citation.epage197
dc.citation.other58: 179-197
dc.citation.rankM21
dc.identifier.wos000345406600027
dc.identifier.doi10.1016/j.exger.2014.08.005
dc.identifier.pmid25128713
dc.identifier.scopus2-s2.0-84907317895
dc.identifier.rcubconv_3207
dc.type.versionpublishedVersion


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