title: Ovarian hormone level alterations during rat post-reproductive life-span influence CD8 + T-cell homeostasis.
abstract: The study examined the putative role of ovarian hormones in shaping of rat peripheral T-cell compartment during post-reproductive period. In 20-month-old rats ovariectomized (Ox) at the very end of reproductive period, thymic output, cellularity and composition of major TCRαβ + peripheral blood lymphocyte and splenocyte subsets were analyzed. Ovariectomy led to the enlargement of CD8 + peripheral blood lymphocyte and splenocyte subpopulations. This reflected: (i) a more efficient thymic generation of CD8 + cells as indicated by increased number of CD4+CD8 + double positive and the most mature CD4-CD8+TCRαβ(high) thymocytes and CD8 + recent thymic emigrants (RTEs) in peripheral blood, but not in the spleen of Ox rats, and (ii) the expansion of CD8 + memory/activated peripheral blood lymphocytes and splenocytes. The latter was consistent with a greater frequency of proliferating cells among freshly isolated memory/activated CD8 + peripheral blood lymphocytes and splenocytes and increased proliferative response of CD8 + splenocytes to stimulation with plate-bound anti-CD3 antibody. The former could be related to the rise in splenic IL-7 and IL-15 mRNA expression. Although ovariectomy affected the overall number of CD4 + T cells in none of the examined compartments, it increased CD4+FoxP3 + peripheral blood lymphocyte and splenocyte counts by enhancing their generation in periphery. Collectively, the results suggest that ovariectomy-induced long-lasting disturbances in ovarian hormone levels (mirrored in diminished progesterone serum level in 20-month-old rats) affects both thymic CD8 + cell generation and peripheral homeostasis and leads to the expansion of CD4+FoxP3 + cells in the periphery, thereby enhancing autoreactive cell control on account of immune system efficacy to combat infections and tumors.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 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", 11221 Belgrade, Serbia.
authors.forename: Duško
authors.initials: D
authors.lastname: Kosec
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, 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", 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, 11221 Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stojić-Vukanić
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Djikić
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Bufan
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia gordana.leposavic@pharmacy.bg.ac.rs.
authors.forename: Gordana
authors.initials: G
authors.lastname: Leposavić
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D004967:Estrogens / Q000097:blood*; D005260:Female; D006706:Homeostasis; D015851:Interleukin-7 / Q000378:metabolism; D018655:Lymphocyte Count; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism*; D011374:Progesterone / Q000097:blood*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012098:Reproduction; D013154:Spleen / Q000378:metabolism
chemical_list: D004967:Estrogens; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011374:Progesterone
keywords: Ovarian gland hormones; T-cell proliferation/apoptosis; mature naïve T cells; memory/activated T cells; regulatory T cells