title: Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats.
abstract: To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+ T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+ T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+ regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+ T lymphocytes, including highly pathogenic IL-17+IFN-γ+ ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+ T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+ cells (reflecting downregulated expression of IL-1β, IL-6 and IL-23/p19). On the other hand, when the neurological deficit reached maximum/plateau, in AO rat spinal cord was found lower CD4+FoxP3+CD25+ cell frequency followed by higher frequency of IL-10-producing CD8+ T cells, which most likely also belong to regulatory T lymphocytes. Thus, the altered relation between regulatory T cell and effector CD4+ T cell subsets was linked with persistence of mild neuroinflammation in AO rat EAE model.
authors.affiliation: Department of Physiology, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Nacka-Aleksić
authors.affiliation: Department of Microbiology and Immunology, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stojić-Vukanić
authors.affiliation: Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pilipović
authors.affiliation: Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Vujnović
authors.affiliation: Department of Microbiology and Immunology, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Bufan
authors.affiliation: Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Dimitrijević
authors.affiliation: Department of Physiology, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia. Electronic address: Gordana.Leposavic@pharmacy.bg.ac.rs.
authors.forename: Gordana
authors.initials: G
authors.lastname: Leposavić
mesh_terms: D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013045:Species Specificity; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2
keywords: Aged rats; EAE; IL-10-producing T cells; IL-17+IFN-γ+ T lymphocytes; Rat strain differences