The β-catenin–TCF-1 pathway ensures CD4+CD8+ thymocyte survival

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Abstract
The association of trans-acting T cell factors (TCFs) or lymphoid enhancer factor 1 (LEF-1) 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-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-xL. 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 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.