The beta-catenin--TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival.

The association of trans-acting T cell factors (TCFs) or lymphoid enhancer factor 1 (LEF-1) with their coactivator beta-catenin mediates transient transcriptional responses to extracellular Wnt signals. We show here that T cell maturation depends on the presence of the beta-catenin--binding domain in TCF-1. This domain is necessary to mediate the survival of immature CD4(+)CD8(+) double-positive (DP) thymocytes. Accelerated spontaneous thymocyte death in the absence of TCF-1 correlates with aberrantly low expression of the anti-apoptotic protein Bcl-x(L). Increasing anti-apoptotic effectors in thymocytes by the use of a Bcl-2 transgene rescued TCF-1-deficient DP thymocytes from apoptosis. Thus, TCF-1, upon association with beta-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) alpha chains and attempt TCR-mediated positive selection.