Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency |
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Authors: | Gordana Leposavić Milica Perišić Nanut Ivan Pilipović Duško Kosec Nevena Arsenović-Ranin Zorica Stojić-Vukanić Jasmina Djikić Mirjana Nacka-Aleksić |
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Institution: | 1. Department of Physiology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia;2. Immunology Research Centre “Branislav Jankovi?”, Institute of Virology, Vaccines and Sera, “Torlak”, 458 Vojvode Stepe, 11221 Belgrade, Serbia;3. Department of Microbiology and Immunology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia |
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Abstract: | This study explores the role of ovarian hormones in the phenotypic shaping of peripheral T-cell pool over the reproductive lifespan of rats. For this purpose, 2-month-old prepubertally ovariectomised (Ox) rats, showing oestrogen and progesterone deficiency, and 11-month-old Ox rats, exhibiting only progesterone deficiency, were examined for thymus output, and cellularity and composition of major TCRαβ+ peripheral blood lymphocyte (PBL) and splenocyte subsets. Although ovariectomy increased thymic output in both 2- and 11-month-old rats, the count of both CD4+ and CD8+ PBLs and splenocytes increased only in the former. In the blood and spleen of 11-month-old Ox rats only the count of CD8+ cells increased. Although ovariectomy affected the total CD4+ count in none of the examined compartments from the 11-month-old rats, it increased CD4+FoxP3+ PBL and splenocyte relative proportions over those in the age-matched controls. The age-related differences in the cellularity and the major subset composition in Ox rats were linked to the differences in the ovarian steroid hormone levels registered in 2- and 11-month-old rats. The administration of progesterone to Ox rats during the seven days before the sacrificing confirmed contribution of this hormone deficiency to the ovariectomy-induced changes in the TCRαβ+ PBL and splenocyte pool from 11-month-old rats. The expansion of the CD8+ splenocyte subset in the 11-month-old Ox rats reflected increases in cellularity of memory and, particularly, naïve cells. This was due to greater thymic output of CD8+ cells and homeostatic proliferation than apoptosis in 11-month-old Ox rats when compared with age-matched sham-Ox control rats. The homeostatic changes within CD8+ splenocyte pool from 11-month-old Ox rats, most likely, reflected the enhanced splenic IL-7 and TGF-β mRNA expression. Overall, in adult female rats, circulating oestrogen and progesterone provide maintenance of T-cell counts, a diversity of T-cell repertoire, and the main T-cell subset composition in the periphery. Progesterone deficiency affects mainly the CD8+ lymphocyte compartment through increasing thymic CD8+ cell export and upsetting homeostatic regulation within the CD8+ splenocyte pool. These alterations were reversible through progesterone supplementation. |
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Keywords: | AO Albino Oxford 7-AAD 7-amino-actinomycin D BSA bovine serum albumin DDM doublet discrimination module DTH delayed-type hypersensitivity FCA flow cytometric analysis FITC fluorescein isothiocyanate FCS fetal calf serum FoxP3 forkhead box P3 FSC forward scatter IFN-γ interferon-γ IL interleukin mAbs monoclonal antibodies MACS magnetic-activated cell sorting mRNA messenger ribonucleic acid NK natural killer Ox ovariectomised PCR polymerase chain reaction PBLs peripheral blood lymphocytes PBS phosphate-buffered saline PE phycoerythrin PerCP peridinin chlorophyll protein RTEs recent thymic emigrants SSC side scatter TGF-β transforming growth factor-β |
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