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首页> 外文期刊>Nature immunology >Rapid effector function of memory CD8~+ T cells requires an immediate-early glycolytic switch
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Rapid effector function of memory CD8~+ T cells requires an immediate-early glycolytic switch

机译：内存CD8〜+ T细胞的快速效应功能需要立即早期的糖浆开关

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摘要

Antigen-experienced memory T cells acquire effector function with innate-like kinetics; however, the metabolic requirements of these cells are unknown. Here we show that rapid interferon-gamma (IFN-gamma) production of effector memory (EM) CD8~+ T cells, activated through stimulation mediated by the T cell antigen receptor (TCR) and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. EM CD8~+ T cells exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early time points, before proliferation commenced, than did naive cells activated under similar conditions. CD28 signaling via the serine-threonine kinase Akt and the metabolic-checkpoint kinase mT0RC2 was needed to sustain TCR-mediated immediate-early glycolysis. Unlike glycolysis in proliferating cells, immediate-early glycolysis in memory CD8~+ T cells was rapamycin insensitive. Thus, CD8~+ memory T cells have an Akt-dependent 'imprinted' glycolytic potential that is required for efficient immediate-early IFN-gamma recall responses.
机译：抗原经验的内存T细胞采用先天式动力学获取效应函数;然而，这些细胞的代谢要求未知。在这里，我们表明，通过由T细胞抗原受体（TCR）介导的刺激和共刺激受体CD28或通过同源相互作用介导的刺激活性记忆（EM）CD8〜+ T细胞的快速干扰素-γ（IFN-Gamma）生产链接至增加糖酵解通量。在进入开始之前，EM CD8〜+ T细胞在早期观点显示出更多的甘氨醛-3-磷酸脱氢酶（GAPDH）活性，比在类似条件下激活的幼稚细胞。通过丝氨酸苏氨酸激酶AKT和代谢检查点激酶MT0RC2需要CD28信号传导，以维持TCR介导的即时 - 早期糖酵解。与增殖细胞中的糖酵解不同，在记忆CD8〜+ T细胞中立即早期的糖酵解是雷帕霉素不敏感的。因此，CD8〜+内存T细胞具有依赖于依赖性的'印迹的'糖型溶解潜力，这是有效立即初期的IFN-Gamma召回反应所必需的。

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