β-连环蛋白–TCF-1信号通路确保CD4(+)CD8(+)胸腺细胞存活。

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

作者信息

Ioannidis V, Beermann F, Clevers H, Held W

机构信息

Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Switzerland.

出版信息

Nat Immunol. 2001 Aug;2(8):691-7. doi: 10.1038/90623.

DOI:10.1038/90623

PMID:11477404

Abstract

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.

摘要

反式作用T细胞因子（TCFs）或淋巴样增强因子1（LEF-1）与其共激活因子β-连环蛋白的结合介导了对细胞外Wnt信号的瞬时转录反应。我们在此表明，T细胞成熟依赖于TCF-1中β-连环蛋白结合结构域的存在。该结构域对于介导未成熟CD4(+)CD8(+)双阳性（DP）胸腺细胞的存活是必需的。在缺乏TCF-1的情况下，胸腺细胞加速自发死亡与抗凋亡蛋白Bcl-x(L)的异常低表达相关。通过使用Bcl-2转基因增加胸腺细胞中的抗凋亡效应分子，可使缺乏TCF-1的DP胸腺细胞免于凋亡。因此，TCF-1与β-连环蛋白结合后，可瞬时确保未成熟T细胞的存活，使其能够生成和编辑T细胞受体（TCR）α链，并尝试进行TCR介导的阳性选择。