Glucose availability regulates IFN-γ production and p70S6 kinase activation in CD8+ effector T cells
Glucose availability regulates IFN-γ production and p70S6 kinase activation in CD8+ effector T cells
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DOI：
10.4049/jimmunol.174.8.4670
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Gajewski, TF
中科院分区：
文献类型：
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作者：
Cham, CM;Gajewski, TF
从初始状态到效应状态的CD8(+) T细胞分化伴随着基础基因表达谱的变化，这些变化与效应功能的获得平行。其中包括代谢基因，我们现在表明，与初始细胞相比，2C TCR转基因效应CD8(+) T细胞表达更高水平的糖酵解酶，并且显示出更高的葡萄糖摄取、更高的糖酵解速率以及增加的乳酸产生。为了确定葡萄糖是否是效应T细胞功能所必需的，我们在体外调节葡萄糖的可利用性。葡萄糖剥夺强烈抑制IFN -γ基因表达，而IL - 2的产生几乎不受影响。这种抑制与p70S6激酶和eIF4E结合蛋白1的磷酸化减少以及对从头蛋白质合成的需求相关，而已知的其他调节IFN -γ表达的信号通路不受影响。总之，我们的数据表明，IFN -γ转录的最佳诱导是一个葡萄糖依赖的过程，提示存在影响IFN -γ表达的未确定因素，并且对组织微环境中CD8(+) T细胞应答的效应阶段的调节具有意义。《免疫学杂志》，2005年，174卷：4670 - 4677页
Differentiation of CD8(+) T cells from the naive to the effector state is accompanied by changes in basal gene expression profiles that parallel the acquisition of effector functions. Among these are metabolism genes, and we now show that 2C TCR transgenic effector CD8(+) T cells express higher levels of glycolytic enzymes and display greater glucose uptake, a higher glycolytic rate, and increased lactate production compared with naive cells. To determine whether glucose was required for effector T cell functions, we regulated glucose availability in vitro. Glucose deprivation strongly inhibited IFN-,gamma gene expression, whereas IL-2 production was little affected. Inhibition correlated with diminished phosphorylation of p70S6 kinase and eIF4E binding protein 1 and a requirement for de novo protein synthesis, whereas other signaling pathways known to regulate IFN-gamma expression were unaffected. Together, our data reveal that optimal induction of IFN-gamma transcription is a glucose-dependent process, indicate that there are undefined factors that influence IFN-gamma expression, and have implications for regulation of the effector phase of CD8(+) T cell responses in tissue microenvironments. The Journal of Immunology, 2005, 174: 4670-4677.