近日，加拿大麦吉尔大学Russell G. Jones及其课题组，使用稳定同位素追踪代谢谱揭示了生理激活的CD8阳性T细胞利用葡萄糖的不同模式。这一研究成果于2019年11月19日发表在国际学术期刊《免疫》上。

研究人员结合了生物能谱分析和¹³C-葡萄糖输注技术来研究响应李斯特菌感染的CD8阳性T细胞的代谢。与具有瓦博格代谢特征的体外活化T细胞相反，生理活化的CD8阳性T细胞具有更高的氧化代谢速率、更高的生物能含量、丙酮酸的不同用途以及¹³C-葡萄糖碳向合成代谢途径的显著流动，包括核苷酸和丝氨酸的生物合成。

磷酸甘油酸脱氢酶介导的葡萄糖依赖性丝氨酸生物合成对于体内CD8阳性T细胞扩增至关重要。这些数据强调了病原体特异性T细胞在体内使用葡萄糖的基本差异，说明了环境对T细胞代谢表型的影响。

据介绍，初始CD8阳性T细胞分化为效应T细胞，从而增加葡萄糖摄取，并从静止代谢转变为合成代谢。尽管对培养的T细胞的代谢了解甚多，但在体内免疫反应期间T细胞如何利用营养物的定义尚不清楚。

附：英文原文

Title: Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells

Author: Eric H. Ma, Mark J. Verway, Radia M. Johnson, Dominic G. Roy, Mya Steadman, Sebastian Hayes, Kelsey S. Williams, Ryan D. Sheldon, Bozena Samborska, Penelope A. Kosinski, Hyeryun Kim, Takla Griss, Brandon Faubert, Stephanie A. Condotta, Connie M. Krawczyk, Ralph J. DeBerardinis, Kelly M. Stewart, Martin J. Richer, Victor Chubukov, Thomas P. Roddy, Russell G. Jones

Issue&Volume: 2019/11/19

Abstract: 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 13C-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 13C-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.

DOI: 10.1016/j.immuni.2019.09.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30374-7