Lymphopenia-Driven Homeostatic Regulation of Naive T Cells in Elderly and Thymectomized Young Adults

Abstract

Reduced thymopoiesis and continuous mobilization of naive T cells into the effector-memory pool can lead to severe alterations of the naive T cell compartment. However, maintenance of the naive T cell population is essential to mount effective immune responses. Evidence of homeostatic regulation of naive T cells is currently debated in animal models. In humans, the situation remains unresolved, in particular with advanced age. In this study, we analyzed the CD4(+) and CD8(+) naive T cell compartments from elderly, young adults thymectomized during early childhood, and HIV-1-infected patients, which are characterized by T lymphocytopenia. We show a direct association between increased turnover and decreased frequency of naive T cells. Moreover, the IL-7-induced pathway was fully functional in naive T cells from elderly and young adults thymectomized during early childhood, who are characterized by elevated IL-7 plasma levels. Our findings support the establishment of homeostatic regulation of naive T cell proliferation in humans. This regulation is particularly active in lymphopenic hosts, such as elderly and thymectomized patients.