title: Sexual dimorphism in the aged rat CD4+ T lymphocyte-mediated immune response elicited by inoculation with spinal cord homogenate.
abstract: Considering the crucial pathogenic role of CD4+ T cells in experimental autoimmune encephalomyelitis (EAE) and the opposite direction of the sexual dimorphism in the severity of the disease in 22-24-and 3-month-old dark agouti rats, sex differences in CD4+ T-cell-mediated immune response in aged rats immunized for EAE were examined and compared with those in young animals. In the inductive phase of EAE, fewer activated CD4+ lymphocytes were retrieved from draining lymph nodes of male (developing less severe disease) compared with female rats, due, at least partly, to their lesser expansion. The former reflected a greater suppressive capacity of CD4+CD25+Foxp3+ cells. Consequently, CD4+ lymphocyte infiltration into the spinal cord of aged male rats was diminished. At the peak of EAE, the frequency of reactivated cells was lower, whereas that of the regulatory CD4+ cells was higher in male rat spinal cord. Consistently, microglial activation and the expression of proinflammatory/damaging cytokines in male rat spinal cord mononuclear cells were diminished. Additionally, the frequency of the highly pathogenic IL-17+IFN-γ+ T lymphocytes infiltrating their spinal cord was lower. Together, these results point to (i) an age-specificity in CD4+ cell-mediated immune response and (ii) mechanisms underlying the sex differences in this response in aged rats.
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Nacka-Aleksić
authors.affiliation: Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pilipović
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stojić-Vukanić
authors.affiliation: Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Duško
authors.initials: D
authors.lastname: Kosec
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Bufan
authors.affiliation: Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Vujnović
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Arsenović-Ranin
authors.affiliation: Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Dimitrijević
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 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; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular; D008297:Male; D051381:Rats; D012727:Sex Characteristics; D013116:Spinal Cord; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
keywords: Aging; CD4+CD25+Foxp3+ lymphocytes; EAE; IL-17+IFN-γ+ lymphocytes; Sexual dimorphism