TCR and IL-7 signaling promote CHMP5 expression in mature αβ T cells. Conditional deletion of Chmp5 in post-thymic T cells is associated with oxidative stress, increased apoptosis, and marked depletion of the peripheral naïve T-cell pool, supporting a critical role for CHMP5 in mediating peripheral T-cell homeostasis.
ABSTRACT
A diverse repertoire of naïve αβ T cells in the periphery is essential for adaptive immunity to pathogens and cancers, as well as for tissue homeostasis. This peripheral T cell pool is maintained by signals from the T cell receptor (TCR) and interleukin-7 (IL-7). However, the mechanisms and downstream factors induced by these signals to support peripheral T cell survival are still not fully understood. We found that TCR and IL-7 signals posttranscriptionally promoted expression of the charged multivesicular body protein 5 (CHMP5) in naïve CD4+ and CD8+ T cells, in which CHMP5 functions to prevent oxidative stress and apoptosis. Consequently, inactivation of the Chmp5 gene in post-thymic T cells resulted in severe depletion of the peripheral T cell pool by a cell-intrinsic mechanism. Collectively, our results suggest that induction of CHMP5 by homeostatic TCR and IL-7 signals is part of a critical mechanism governing naïve T cell homeostasis in the periphery.