The β-catenin-TCF-I pathway ensures CD4+CD8+ thymocyte survival
The β-catenin-TCF-I pathway ensures CD4+CD8+ thymocyte survival
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DOI：
10.1038/90623
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发表时间：
2001-08-01
影响因子：
30.5
通讯作者：
Held, W
中科院分区：
文献类型：
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作者：
Ioannidis, V;Beermann, F;Held, W
反式激活T细胞因子（TCF）或淋巴增强因子I（LEF-I）与它们的共激活因子β-连环蛋白的结合介导对细胞外Wnt信号的瞬时转录应答。我们在这里表明，T细胞成熟依赖于TCF-1中β-连环蛋白结合结构域的存在。该结构域是介导未成熟的CD 4 + CD 8+双阳性（DP）胸腺细胞存活所必需的。TCF-I缺乏时胸腺细胞自发性加速死亡与抗凋亡蛋白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子，可使TCF-I缺陷型DP胸腺细胞免于凋亡。因此，TCF-I在与β-连环蛋白缔合后瞬时确保未成熟T细胞的存活，这使得它们能够产生和编辑T细胞受体（TCR）α链并尝试TCR介导的阳性选择。
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.