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

The association of trans-acting T cell factors (TCFs) or lymphoid enhancer factor I (LEF-I) with their coactivator β-catenin mediates transient transcriptional responses to extracellular Wnt signals. We show here that T cell maturation depends on the presence of the β-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 β-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) α chains and attempt TCR-mediated positive selection.