CD28
细胞生物学
效应器
糖酵解
生物
细胞毒性T细胞
mTORC1型
CD8型
T细胞受体
T细胞
PI3K/AKT/mTOR通路
抗原
信号转导
生物化学
免疫学
免疫系统
新陈代谢
体外
作者
Patrick M. Gubser,Glenn R. Bantug,Leyla Razik,Marco Fischer,Sarah Dimeloe,Gideon Höenger,Bojana Müller-Durovic,Annaïse Jauch,Christoph Hess
出处
期刊:Nature Immunology
[Nature Portfolio]
日期:2013-08-18
卷期号:14 (10): 1064-1072
被引量:472
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-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.
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