Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: a putative role for progesterone deficiency.
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.
Department of Physiology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia. Electronic address: Gordana.Leposavic@pharmacy.bg.ac.rs.
Gordana
G
Leposavić
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera, "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Milica Perišić
MP
Nanut
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera, "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Ivan
I
Pilipović
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera, "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Duško
D
Kosec
Department of Microbiology and Immunology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Nevena
N
Arsenović-Ranin
Department of Microbiology and Immunology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Zorica
Z
Stojić-Vukanić
Department of Physiology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Jasmina
J
Djikić
Department of Physiology, University of Belgrade, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Mirjana
M
Nacka-Aleksić
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004967:Estrogens / Q000172:deficiency / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007156:Immunologic Memory; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism; D011374:Progesterone / Q000172:deficiency / Q000276:immunology*; D011627:Puberty; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012098:Reproduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004967:Estrogens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011374:Progesterone
7-AAD; 7-amino-actinomycin D; AO; Albino Oxford; BSA; DDM; DTH; FCA; FCS; FITC; FSC; FoxP3; IFN-γ; IL; Immunoregulatory cytokines; MACS; NK; Ox; PBLs; PBS; PCR; PE; PerCP; Peripheral blood lymphocytes; Progesterone; RTEs; Reproductive lifespan; SSC; Splenocytes; T-cell subsets; TGF-β; bovine serum albumin; delayed-type hypersensitivity; doublet discrimination module; fetal calf serum; flow cytometric analysis; fluorescein isothiocyanate; forkhead box P3; forward scatter; interferon-γ; interleukin; mAbs; mRNA; magnetic-activated cell sorting; messenger ribonucleic acid; monoclonal antibodies; natural killer; ovariectomised; peridinin chlorophyll protein; peripheral blood lymphocytes; phosphate-buffered saline; phycoerythrin; polymerase chain reaction; recent thymic emigrants; side scatter; transforming growth factor-β