β-Catenin/Tcf Determines the Outcome of Thymic Selection in Response to αβTCR Signaling

Abstract

Thymic maturation of T cells depends on the intracellular interpretation of αβTCR signals by processes that are poorly understood. In this study, we report that β-catenin/Tcf signaling was activated in double-positive thymocytes in response to αβTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of β-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-xL were alternatively influenced by stabilization of β-catenin or ablation of Tcf-1, and Bim-mediated β-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized β-catenin triggered signaling associated with negative selection, including sustained overactivation of Lat and Jnk and a transient activation of Erk. These observations are consistent with β-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the αβTCR cascade.