Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1.
Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1.
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DOI：
10.1016/j.immuni.2010.08.002
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发表时间：
2010-08-27
期刊：
影响因子：
32.4
通讯作者：
Xue HH
中科院分区：
文献类型：
--
作者：
Zhou X;Yu S;Zhao DM;Harty JT;Badovinac VP;Xue HH
T细胞因子1（TCF-1）是已知在经典Wnt途径下游起作用的转录因子，并且对于正常T细胞发育是必需的。然而，其在成熟CD8 + T细胞应答中的生理作用尚不清楚。在这里，我们发现TCF-1缺陷限制了CD8+效应T细胞的增殖，并损害了它们向中枢记忆表型的分化。此外，TCF-1缺陷型记忆性CD8 + T细胞随着时间的推移逐渐丢失，表现出抗凋亡分子Bcl-2、白细胞介素-2受体β链的表达减少以及IL-15驱动的增殖减少。TCF-1与Eomes等位基因直接相关，Wnt-TCF-1通路对于初始和记忆性CD8 + T细胞中Eomes的最佳表达是必要和充分的。重要的是，Eomes的强制表达部分保护TCF-1缺陷型记忆性CD8 + T细胞免受时间依赖性磨损。因此，我们的研究确定TCF-1作为一个关键的球员在转录程序，调节记忆CD8分化和寿命。
T cell factor 1 (TCF-1) is a transcription factor known to act downstream of the canonical Wnt pathway and is essential for normal T cell development. However, its physiological roles in mature CD8+ T cell responses are unknown. Here we showed that TCF-1 deficiency limited proliferation of CD8+ effector T cells and impaired their differentiation towards a central memory phenotype. Moreover, TCF-1-deficient memory CD8+ T cells were progressively lost over time, exhibiting reduced expression of the anti-apoptotic molecule Bcl-2, interleukin-2 receptor β chain and diminished IL-15-driven proliferation. TCF-1 was directly associated with the Eomes allele and the Wnt-TCF-1 pathway was necessary and sufficient for optimal Eomes expression in naïve and memory CD8+ T cells. Importantly, forced expression of Eomes partly protected TCF-1-deficient memory CD8+ T cells from time-dependent attrition. Our studies thus identify TCF-1 as a critical player in a transcriptional program that regulates memory CD8 differentiation and longevity.
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