Control of T Cell Development In Vivo by Subdomains Within the IL-7 Receptor α-Chain Cytoplasmic Tail

Abstract

IL-7/IL-7R signaling functions in both growth and differentiation during T cell development. In this study, we examined the extent these activities were controlled by signaling associated with distinct IL-7Rα cytoplasmic domains by transgenic expression of wild-type or cytoplasmic deletion mutants of IL-7Rα in the thymi of IL-7Rα−/− mice. We show an essential requirement for the tyrosine-containing carboxyl-terminal T domain in restoring thymic cellularity, pro-/pre-T cell progression, and survival. In contrast, the functional differentiation of TCR αβ cells and the development of TCR γδ cells are partially independent of the T domain. Thus, separate cytoplasmic domains of the IL-7Rα chain differentially control distinct functions during T cell development, whereas normal IL-7R-dependent thymic development requires the integrated activity of all these domains.