Abstract
Naive CD8+ Tcells differentiating into effector Tcells increase glucose uptake and shift from quiescent to anabolic metabolism. Although much is known about the metabolism of cultured Tcells, how Tcells use nutrients during immune responses invivo is less well defined. Here, we combined bioenergetic profiling and 13C-glucose infusion techniques to investigate the metabolism of CD8+ Tcells responding to Listeria infection. In contrast to invitro-activated Tcells, which display hallmarks of Warburg metabolism, physiologically activated CD8+ Tcells 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+ Tcell expansion invivo. Our data highlight fundamental differences in glucose use by pathogen-specific Tcells invivo, illustrating the impact of environment on Tcell metabolic phenotypes.
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