Carbon source availability drives nutrient utilization in CD8+ T cells

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)1298-1311.e6
JournalCell Metabolism
Volume34
Issue number9
DOIs
StatePublished - Sep 6 2022

Keywords

  • C tracing
  • immunometabolism
  • lactate
  • metabolic programming
  • metabolomics
  • T cells
  • TCA cycle

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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