Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells
Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells
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DOI：
10.1016/j.immuni.2019.09.003
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发表时间：
2019-11-19
期刊：
影响因子：
32.4
通讯作者：
Jones, Russell G.
中科院分区：
文献类型：
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作者：
Ma, Eric H.;Verway, Mark J.;Jones, Russell G.
幼稚CD 8（+）T细胞分化为效应T细胞增加葡萄糖摄取并从静止代谢转变为合成代谢。虽然对培养的T细胞的代谢有很多了解，但T细胞在体内免疫反应期间如何使用营养素还不太清楚。在这里，我们结合生物能量分析和C-13-葡萄糖输注技术来研究响应李斯特菌感染的CD 8（+）T细胞的代谢。与体外活化的T细胞（显示出瓦尔堡代谢的特征）相反，生理活化的CD 8（+）T细胞显示出更高的氧化代谢速率、更高的生物能量能力、丙酮酸的差异使用以及C-13-葡萄糖碳向合成代谢途径（包括核苷酸和丝氨酸生物合成）的显著流动。由Phgdh酶介导的葡萄糖依赖性丝氨酸生物合成对于体内CD 8（+）T细胞扩增至关重要。我们的数据突出了病原体特异性T细胞在体内使用葡萄糖的根本差异，说明了环境对T细胞代谢表型的影响。
Naive CD8(+) T cells differentiating into effector T cells increase glucose uptake and shift from quiescent to anabolic metabolism. Although much is known about the metabolism of cultured T cells, how T cells use nutrients during immune responses in vivo is less well defined. Here, we combined bioenergetic profiling and C-13-glucose infusion techniques to investigate the metabolism of CD8(+) T cells responding to Listeria infection. In contrast to in vitro-activated T cells, which display hallmarks of Warburg metabolism, physiologically activated CD8(+) T cells displayed greater rates of oxidative metabolism, higher bioenergetic capacity, differential use of pyruvate, and prominent flow of C-13-glucose carbon to anabolic pathways, including nucleotide and serine biosynthesis. Glucose-dependent serine biosynthesis mediated by the enzyme Phgdh was essential for CD8(+) T cell expansion in vivo. Our data highlight fundamental differences in glucose use by pathogen-specific T cells in vivo, illustrating the impact of environment on T cell metabolic phenotypes.