1] Department of Biomedicine, Immunobiology, University of Basel, Basel, Switzerland. [2].
Nat Immunol. 2013 Oct;14(10):1064-72. doi: 10.1038/ni.2687. Epub 2013 Aug 18.
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-γ (IFN-γ) 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 mTORC2 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-γ recall responses.
有经验的抗原记忆 T 细胞获得了类似先天的效应功能；然而，这些细胞的代谢需求尚不清楚。在这里，我们表明，通过 T 细胞抗原受体 (TCR) 和共刺激受体 CD28 介导的刺激或通过同源相互作用激活的效应记忆 (EM) CD8(+) T 细胞，干扰素-γ (IFN-γ) 的快速产生与增加的糖酵解通量有关。与在类似条件下激活的幼稚细胞相比，在开始增殖之前，早期的 EM CD8(+) T 细胞具有更高的甘油醛-3-磷酸脱氢酶 (GAPDH) 活性。通过丝氨酸-苏氨酸激酶 Akt 和代谢检查点激酶 mTORC2 的 CD28 信号传导对于维持 TCR 介导的早期糖酵解是必需的。与增殖细胞中的糖酵解不同，记忆 CD8(+) T 细胞中的早期糖酵解对雷帕霉素不敏感。因此，CD8(+)记忆 T 细胞具有 Akt 依赖性的“印迹”糖酵解潜力，这对于有效的早期 IFN-γ 回忆反应是必需的。
