IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice

Significance In mammals, regulatory T cells establish and maintain immune responses toward self- and non–self-antigens by suppression of specific T cells. Several mechanisms of suppression were previously described including starvation for IL-2, a cytokine required for T-cell expansion. Here we show that regulatory T cells (T reg ) respond to IL-7, a T-cell survival factor produced by lymph node fibroblast reticular cells, by enhancing their IL-2 sensitivity, thereby limiting expansion of reactive T cells during inflammation. These findings highlight a previously unidentified and unexpected mechanism by which IL-7R signaling in T reg cells maintains peripheral and allograft tolerance. This work may contribute to design new therapeutic approaches using lower IL-2 doses in humans by enhancing the functional competence of regulatory T cells with IL-7.