THE COMMON GAMMA-CHAIN OF CYTOKINE RECEPTORS REGULATES INTRATHYMIC T-CELL DEVELOPMENT AT MULTIPLE STAGES

Signaling through the common gamma chain (gamma c), a subunit of the r eceptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte dev elopment, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cell development that are d ependent on gamma c and to determine whether gamma c controls T cell d evelopment solely as a component of the IL-7R, intrathymic T tell deve lopment was compared in IL-7R alpha-deficient mice and anti-gamma c-tr eated chimeric mice reconstituted with bone marrow and purified pro-T cells. In the presence of anti-gamma c, each of four phenotypically di stinguishable stages of CD4(-)CD8(-) thymocytes failed to reconstitute T cell development, suggesting that each of these subsets of pro-T ce lls required gamma c for their differentiation and/or growth. Reconsti tution of anti-gamma c-treated chimeric mice with bone marrow from IL- 7R alpha-deficient mice indicated that IL-7R only partially contribute d to intrathymic T cell development. Furthermore, when compared with I L-7R-deficient mice, anti-gamma c chimeric and gamma c-deficient mice exhibited a distinct phenotypic pattern of pro-T cell development. Col lectively, these results indicate that several gamma c-sharing cytokin es may contribute to T cell development in the thymus and suggest that one of these cytokines may be novel.