Control of T cell development in vivo by subdomains within the IL-7 receptor alpha-chain cytoplasmic tail

IL-7/IL-7R signaling functions in both growth and differentiation during T cell development. In this study, we examined the extent these activities we re controlled by signaling associated with distinct IL-7R alpha cytoplasmic domains by transgenic expression of wild-type or cytoplasmic deletion muta nts of IL-7R alpha in the thymi of IL-7R alpha (-/-) mice. We show an essen tial 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 alpha beta tells and the d evelopment of TCR gamma delta cells are partially independent of the T doma in. Thus, separate cytoplasmic domains of the IL-7R alpha chain differentia lly control distinct functions during T cell development, whereas normal IL -7R-dependent thymic development requires the integrated activity of all th ese domains.