Cell metabolism · 17 authors, 9 centres
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This preclinical study used stable isotope labeling and in vivo Listeria infection models in mice to show that physiologic carbon sources such as lactate are preferentially oxidized by CD8+ T cells and enhance their bioenergetic and effector function.
They report that CD8+ T cells display mitochondrial fuel plasticity, oxidizing acetate, beta-hydroxybutyrate, and lactate alongside glucose and glutamine. The presence of PCSs reduced glucose contribution to the TCA cycle and enhanced CD8+ T cell effector function, with lactate favored approximately 4-fold over glucose as a TCA cycle substrate in pathogen-specific cells and contributing to pyrimidine and palmitate biosynthesis. Silencing Ldha impaired lactate-to-pyruvate conversion, TCA cycle fueling, and CD8+ T cell proliferative expansion in vivo. Limitations include restriction to PCSs above 100 micromolar, lack of consideration for additional low-abundance metabolites and oxygen availability, and reliance on mouse and in vitro systems. The findings identify lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells and suggest that environmental nutrient availability shapes T cell metabolism.
