Antigen-driven effector CD8 T cell function regulated by T-bet
Antigen-driven effector CD8 T cell function regulated by T-bet
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DOI：
10.1073/pnas.2636938100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
Sullivan, BM;Juedes, A;Glimcher, LH
1 型免疫依赖于 T 淋巴细胞的两个主要亚群的分化，即 CD4(+) T 辅助 (Th) 细胞和 CD8(+) 细胞毒性 T 细胞，它们指导对于破坏细胞内和细胞外病原体至关重要的炎症和细胞毒性反应。与 CD4 细胞相反，人们对控制 CD8 幼稚细胞阶段向效应细胞阶段转变的转录因子知之甚少。在这里，我们报道已知调节 Th 细胞分化的转录因子 T-bet 也控制 CD8(+) 细胞毒性效应细胞的产生。在缺乏 T-bet 的 OT-I T 细胞受体转基因小鼠中，抗原驱动的效应 CD8+ 细胞的产生受到损害，导致细胞毒性减弱和细胞因子分泌谱显着变化。此外，缺乏T-bet的小鼠对淋巴细胞性脉络丛脑膜炎病毒感染的反应较差。 T-bet 在 Th 细胞和 T 细胞毒性细胞中发挥着 1 型免疫生成的关键作用。
Type 1 immunity relies on the differentiation of two major subsets of T lymphocytes, the CD4(+) T helper (Th) cell and the CD8(+) cytotoxic T cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. In contrast to CD4 cells, little is known about transcription factors that control the transition from the CD8 naive to effector cell stage. Here, we report that the transcription factor T-bet, known to regulate Th cell differentiation, also controls the generation of the CD8(+) cytotoxic effector cell. Antigen-driven generation of effector CD8+ cells was impaired in OT-I T cell receptor transgenic mice lacking T-bet, resulting in diminished cytotoxicity and a marked shift in cytokine secretion profiles. Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic choriomeningitis virus. T-bet is a key player in the generation of type 1 immunity, in both Th and T cytotoxic cells.