Enhanced IL-7 responsiveness provides competitive advantage to recent thymic emigrants in peripheral T cell survival and homeostasis (IRC8P.451)

Recent thymic emigrants (RTE) are newly generated T cells that are necessary to replenish T cell antigen receptor diversity and rejuvenate the peripheral naive T cell pool. Both naive T cells and RTE require IL-7 to survive in the periphery, but it is not known how RTE successfully compete with resident T cells for IL-7 signaling. To address this question, we assessed IL-7 receptor (IL-7Ra) expression on RTE, and found that RTE expresse substantially lower levels of IL-7Ra than naive T cells. Because IL-7 signaling downregulates expression of its own receptor, lower IL-7Ra expression suggest that RTE are potentially more responsive to IL-7 than naive T cells. Indeed, in vitro IL-7 stimulation showed significantly increased STAT5 phosphorylation in RTE compared to naive T cells. To understand the molecular basis for increased IL-7 responsiveness, we assessed STAT5 phosphorylation and IL-7R expression upon IL-7 re-stimulation, and found that RTE are significantly more responsive to IL-7 re-stimulation. Contrary, adoptive transfer of RTE cells into lymphopenic host mice resulted in less efficient proliferation and expansion than of naive donor T cells, which was not rescued by increasing in vivo IL-7 levels by implanting IL-7 osmotic pumps. Collectively, these data indicate that increased IL-7 responsiveness in RTE maximizes their survival while decreasing their proliferative capacity such as under lymphopenic conditions.