The combined loss of Gads and CD127 reveals a novel function of Gads prior to TCRβ expression.

The Gads adaptor protein is an essential component of the T cell signaling complex critical for T cell receptor-mediated calcium mobilization. After expression of TCRβ in T cell precursors, Gads is required for optimal Bcl-2 expression and cell survival. Similarly, the IL-7 receptor chain CD127 is also necessary for optimal Bcl-2 expression and cell survival in TCRβ-expressing thymocytes. Based on these observations, we tested whether Gads and CD127 might regulate convergent or linear signaling pathways by crossing Gads(-/-) mice with CD127(-/-) mice. Thymi from Gads(-/-)CD127(-/-) mice were barely detectable and many of the thymocytes were within the DN1 population. By contrast, B cell development in the Gads(-/-)CD127(-/-) mice was comparable to that of CD127(-/-) mice, indicating that the combined loss of Gads and CD127 did not lead to a global deficit in hematopoiesis. Analysis of Lin(-)Sca-1(+)c-kit(+) bone marrow cells and bone marrow chimera experiments indicated that Gads(-/-)CD127(-/-) T cell precursors either failed to migrate into the thymus or survive in the thymus. These data demonstrate that Gads functions at a stage of T cell development that had not been previously described.