Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats
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Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral bl...ood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism.
Keywords:Neonatal androgenization / T-cell differentiation / Peripheral blood T lymphocytes / Recent thymic emigrants
Source:Brain Behavior and Immunity, 2009, 23, 2, 294-304
- Academic Press Inc Elsevier Science, San Diego