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.
Original language | English (US) |
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Pages (from-to) | 1298-1311.e6 |
Journal | Cell Metabolism |
Volume | 34 |
Issue number | 9 |
DOIs | |
State | Published - Sep 6 2022 |
Keywords
- C tracing
- T cells
- TCA cycle
- immunometabolism
- lactate
- metabolic programming
- metabolomics
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology