TGF-? cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor ? expression.

ABSTRACT: Interleukin-7 receptor ? chain (IL-7R?) is induced upon T cell positive selection and controls thymic CD8-lineage specification and peripheral naive T cell homeostasis. How IL-7R? expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor ? (TGF-?) signaling promoted IL-7R? expression and CD8+ T cell differentiation. In addition, TGF-? signaling was required for high IL-7R? expression in CD4+ T cells bearing low-affinity T cell receptors, and the abrogation of TGF-? receptor expression led to failed maintenance of peripheral CD4+ T cells. Compromised IL-7R? expression in TGF-?-receptor-deficient T cells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7R? transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7R? expression and largely ameliorated the development and homeostasis defects of TGF-?-receptor-deficient T cells. These findings reveal functions for TGF-? signaling in controlling IL-7R? expression and in promoting T cell repertoire diversification.

SUBMITTER: Ouyang W 

PROVIDER: S-EPMC3801187 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature