The β-catenin-TCF-I pathway ensures CD4+CD8+ thymocyte survival

The association of trans-actingT cell factors (TCFs) or lymphoid enhancer factor I (LEF-I) 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-I. 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-I 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-I-deficient DP thymocytes from apoptosis. Thus, TCF-I, 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.