The Common γ-Chain of Cytokine Receptors Regulates Intrathymic T Cell Development at Multiple Stages

Signaling through the common γ chain (γc), a subunit of the receptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte development, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cell development that are dependent on γc and to determine whether γc controls T cell development solely as a component of the IL-7R, intrathymic T cell development was compared in IL-7R α-deficient mice and anti-γc-treated chimeric mice reconstituted with bone marrow and purified pro-T cells. In the presence of anti-γc, each of four phenotypically distinguishable stages of CD4^-CD8^- thymocytes failed to reconstitute T cell development, suggesting that each of these subsets of pro-T cells required γc for their differentiation and/or growth. Reconstitution of anti-γc-treated chimeric mice with bone marrow from IL-7R α-deficient mice indicated that IL-7R only partially contributed to intrathymic T cell development. Furthermore, when compared with IL-7R-deficient mice, anti-γc chimeric and γc-deficient mice exhibited a distinct phenotypic pattern of pro-T cell development. Collectively, these results indicate that several γc-sharing cytokines may contribute to T cell development in the thymus and suggest that one of these cytokines may be novel.