Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.
Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.
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DOI：
10.1371/journal.pone.0104104
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Macintyre AN
中科院分区：
文献类型：
--
作者：
Cao Y;Rathmell JC;Macintyre AN
T淋巴细胞（T细胞）在激活后会经历代谢重编程，以便为生长、增殖和分化提供能量及生物合成物质。然而，不同的T细胞亚群会采用特定的代谢程序来满足自身需求。由于CD4 T细胞协调适应性免疫应答，而CD8 T细胞成为细胞毒性效应细胞，我们比较了这些亚群在激活诱导下的增殖和代谢重编程情况。静息的CD4和CD8 T细胞在代谢上相似，主要采用氧化代谢。激活后，CD8 T细胞增殖更为迅速。刺激使CD4和CD8 T细胞的葡萄糖代谢急剧增加，并将有氧糖酵解作为主要代谢程序。然而，激活的CD4 T细胞比激活的CD8 T细胞更具氧化性，且最大呼吸能力更强。无论激活环境如何，CD4 T细胞还与更高水平的活性氧（ROS）和增加的线粒体含量相关。然而，CD8细胞更能将谷氨酰胺作为替代燃料来源进行氧化。激活的CD8 T细胞更偏向糖酵解的代谢方式与生长和增殖能力的增强以及细胞生长对代谢抑制的敏感性降低相关。这些特定的代谢程序可能促进CD8 T细胞更大程度的生长和增殖，并提高其在不同营养条件下的生存能力。
T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
6.4
作者：
Campbell, SB;Komata, T;Kelso, A
通讯作者：
Kelso, A
影响因子：
3.7
作者：
He S;Kato K;Jiang J;Wahl DR;Mineishi S;Fisher EM;Murasko DM;Glick GD;Zhang Y
通讯作者：
Zhang Y
影响因子：
4.4
作者：
Foulds, KE;Zenewicz, LA;Shen, H
通讯作者：
Shen, H