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dc.creatorStojić-Vukanić, Zorica
dc.creatorNacka-Aleksić, Mirjana
dc.creatorPilipović, Ivan
dc.creatorVujnović, Ivana
dc.creatorBlagojević, Veljko
dc.creatorKosec, Duško
dc.creatorDimitrijević, Mirjana
dc.creatorLeposavić, Gordana
dc.date.accessioned2021-02-18T10:44:31Z
dc.date.available2021-02-18T10:44:31Z
dc.date.issued2015
dc.identifier.issn1742-4933
dc.identifier.urihttp://intor.torlakinstitut.com/handle/123456789/430
dc.description.abstractBackground: Aging influences immune response and susceptibility to EAE in a strain specific manner. The study was designed to examine influence of aging on EAE induction in Albino Oxford (AO) rats. Results: Differently from 3-month-old (young) rats, which were resistant to EAE induction, the majority of aged (24-26-month-old) rats developed mild chronic form of EAE. On 16th day post-immunization, when in aged rats the neurological deficit reached plateau, more mononuclear cells, including CD4+ T lymphocytes was retrieved from spinal cord of aged than young rats. The frequencies of IL-17+ and GM-CSF+ cells within spinal cord infiltrating CD4+ lymphocytes were greater in aged rats. To their increased frequency contributed the expansion of GM-CSF + IL-17 + IFN-gamma+ cells, which are highly pathogenic in mice. The expression of the cytokines (IL-1 beta and IL-23/p19) driving GM-CSF + IL-17 + IFN-gamma + cell differentiation in mice was also augmented in aged rat spinal cord mononuclear cells. Additionally, in aged rat spinal cord the expansion of GM-CSF + IL-17-IFN-gamma- CD4+ T lymphocytes was found. Consistently, the expression of mRNAs for IL-3, the cytokine exhibiting the same expression pattern as GM-CSF, and IL-7, the cytokine driving differentiation of GM-CSF + IL-17-IFN-gamma- CD4 + lymphocytes in mice, was upregulated in aged rat spinal cord mononuclear cells, and the tissue, respectively. This was in accordance with the enhanced generation of the brain antigen-specific GM-CSF+ CD4+ lymphocytes in aged rat draining lymph nodes, as suggested by (i) the higher frequency of GM-CSF+ cells (reflecting the expansion of IL-17-IFN-gamma- cells) within their CD4+ lymphocytes and (ii) the upregulated GM-CSF and IL-3 mRNA expression in fresh CD4+ lymphocytes and MBP-stimulated draining lymph node cells and IL-7 mRNA in lymph node tissue from aged rats. In agreement with the upregulated GM-CSF expression in aged rats, strikingly more CD11b + CD45(int) (activated microglia) and CD45(hi) (mainly proinflammatory dendritic cells and macrophages) cells was retrieved from aged than young rat spinal cord. Besides, expression of mRNA for SOCS1, a negative regulator of proinflammatory cytokine expression in innate immunity cells, was downregulated in aged rat spinal cord mononuclear cells. Conclusions: The study revealed that aging may overcome genetic resistance to EAE, and indicated the cellular and molecular mechanisms contributing to this phenomenon in AO rats.en
dc.publisherBMC, London
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceImmunity & Ageing
dc.subjectAO ratsen
dc.subjectAgingen
dc.subjectEAEen
dc.subjectGM-CSFen
dc.titleAging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+T cells in aged ratsen
dc.typearticle
dc.rights.licenseBY
dc.citation.other12
dc.citation.rankM22
dc.citation.volume12
dc.identifier.doi10.1186/s12979-015-0044-x
dc.identifier.fulltexthttp://intor.torlakinstitut.com/bitstream/id/262/427.pdf
dc.identifier.pmid26448779
dc.identifier.rcubconv_370
dc.identifier.scopus2-s2.0-84943429482
dc.identifier.wos000362407400001
dc.type.versionpublishedVersion


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