Sensitivity to Restimulation-Induced Cell Death Is Linked to Glycolytic Metabolism in Human T Cells.
Sensitivity to Restimulation-Induced Cell Death Is Linked to Glycolytic Metabolism in Human T Cells.
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DOI：
10.4049/jimmunol.1601218
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Snow AL
中科院分区：
文献类型：
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作者：
Larsen SE;Bilenkin A;Tarasenko TN;Arjunaraja S;Stinson JR;McGuire PJ;Snow AL
再刺激诱导的细胞死亡(RICD)通过抑制效应T细胞的增殖和限制对宿主的非特异性损伤来调节免疫反应。RICD是由T细胞受体(TCR)在循环效应T细胞上的重新结合而触发的，导致细胞凋亡。目前尚不清楚RICD敏感性是如何在来自不同个体或亚群的T细胞中校准的。在这里，我们表明有氧糖酵解与人类CD8+效应T细胞对RICD的敏感性密切相关。降低糖酵解活性或葡萄糖供应使效应性T细胞对RICD的敏感性显著降低。我们发现，在TCR重新刺激时，主动糖酵解特异性地促进促凋亡的Fas配体的诱导，这是高度糖酵解T细胞对RICD敏感性增强的原因。总而言之，这些数据表明RICD的易感性与代谢重新编程有关，当T细胞过渡到内存池时，切换回代谢静止状态可能有助于保护T细胞免受RICD的影响。
Restimulation-induced cell death (RICD) regulates immune responses by restraining effector T cell expansion and limiting nonspecific damage to the host. RICD is triggered by re-engagement of the T cell receptor (TCR) on a cycling effector T cell, resulting in apoptosis. It remains unclear how RICD sensitivity is calibrated in T cells derived from different individuals or subsets. Here we show that aerobic glycolysis strongly correlates with RICD sensitivity in human CD8+ effector T cells. Reducing glycolytic activity or glucose availability rendered effector T cells significantly less sensitive to RICD. We found that active glycolysis specifically facilitates the induction of pro-apoptotic Fas ligand upon TCR restimulation, accounting for enhanced RICD sensitivity in highly glycolytic T cells. Collectively, these data indicate that RICD susceptibility is linked to metabolic reprogramming, and that switching back to metabolic quiescence may help shield T cells from RICD as they transition into the memory pool.