Carbon source availability drives nutrient utilization in CD8+ T cells

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  • Irem Kaymak
  • Luda, Katarzyna Maria
  • 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

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
JournalCell Metabolism
Volume34
Issue number9
Pages (from-to)1298-1311
Number of pages14
ISSN1550-4131
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

    Research areas

  • (13)C tracing, immunometabolism, lactate, metabolic programming, metabolomics, T cells, TCA cycle

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