美国Van Andel研究所Russell G. Jones团队发现，碳源可用性驱动CD8⁺T细胞的营养利用。2022年8月17日，《细胞—代谢》杂志在线发表了这项成果。

研究人员发现，细胞培养基中生理碳源（PCS）的存在广泛影响了CD8⁺T细胞对葡萄糖的利用，这与代谢重编程的转录变化无关。PCS的存在减少了葡萄糖对TCA循环的贡献，增加了CD8⁺T细胞的效应功能，乳酸直接为TCA循环提供燃料。事实上，对李斯特菌感染作出反应的CD8⁺T细胞在体外优先消耗乳酸而不是葡萄糖作为TCA循环底物，乳酸增强了T细胞的生物能量和生物合成能力。通过沉默乳酸脱氢酶A（Ldha）抑制CD8⁺T细胞的乳酸依赖性代谢，既损害了T细胞的代谢稳态，也损害了体内的增殖扩张。

总之，这些数据表明，碳源的可用性决定了T细胞的葡萄糖代谢，并确定了乳酸是CD8⁺效应T细胞的生物能量和生物合成燃料。

据悉，环境营养物质的可用性如何影响T细胞的代谢和功能仍然知之甚少。

附：英文原文

Title: Carbon source availability drives nutrient utilization in CD8+ T cells

Author: Irem Kaymak, Katarzyna M. Luda, Lauren R. Duimstra, Eric H. Ma, Joseph Longo, Michael S. Dahabieh, Brandon Faubert, Brandon M. Oswald, McLane J. Watson, Susan M. Kitchen-Goosen, Lisa M. DeCamp, Shelby E. Compton, Zhen Fu, Ralph J. DeBerardinis, Kelsey S. Williams, Ryan D. Sheldon, Russell G. Jones

Issue&Volume: 2022-08-17

Abstract: How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8+ T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8+ T cells, with lactate directly fueling the TCA cycle. In fact, CD8+ T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro, with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8+ T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo. Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells.

DOI: 10.1016/j.cmet.2022.07.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00311-4