First Author | Kim HK | Year | 2016 |
Journal | Eur J Immunol | Volume | 46 |
Issue | 7 | Pages | 1669-80 |
PubMed ID | 27129922 | Mgi Jnum | J:246488 |
Mgi Id | MGI:5923884 | Doi | 10.1002/eji.201546214 |
Citation | Kim HK, et al. (2016) Distinct IL-7 signaling in recent thymic emigrants versus mature naive T cells controls T-cell homeostasis. Eur J Immunol 46(7):1669-80 |
abstractText | IL-7 is essential for T-cell survival but its availability is limited in vivo. Consequently, all peripheral T cells, including recent thymic emigrants (RTEs) are constantly competing for IL-7 to survive. RTEs are required to replenish TCR diversity and rejuvenate the peripheral T-cell pool. However, it remains unknown how RTEs successfully compete with resident mature T cells for IL-7. Moreover, RTEs express low levels of IL-7 receptors, presumably rendering them even less competitive. Here, we show that, surprisingly, RTEs are more responsive to IL-7 than mature naive T cells as demonstrated by markedly increased STAT5 phosphorylation upon IL-7 stimulation. Nonetheless, adoptive transfer of RTE cells into lymphopenic host mice resulted in slower IL-7-induced homeostatic proliferation and diminished expansion compared to naive donor T cells. Mechanistically, we found that IL-7 signaling in RTEs preferentially upregulated expression of Bcl-2, which is anti-apoptotic but also anti-proliferative. In contrast, naive T cells showed diminished Bcl-2 induction but greater proliferative response to IL-7. Collectively, these data indicate that IL-7 responsiveness in RTE is designed to maximize survival at the expense of reduced proliferation, consistent with RTE serving as a subpopulation of T cells rich in diversity but not in frequency. |