Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells

Eric H. Ma, Mark J. Verway, Radia M. Johnson, Dominic G. Roy, Mya Steadman, Sebastian Hayes, Kelsey S. Williams, Ryan D. Sheldon, Bozena Samborska, Penelope A. Kosinski, Hyeryun Kim, Takla Griss, Brandon Faubert, Stephanie A. Condotta, Connie M. Krawczyk, Ralph J. DeBerardinis, Kelly M. Stewart, Martin J. Richer, Victor Chubukov, Thomas P. RoddyRussell G. Jones

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Naive CD8+ T cells differentiating into effector T cells increase glucose uptake and shift from quiescent to anabolic metabolism. Although much is known about the metabolism of cultured T cells, how T cells use nutrients during immune responses in vivo is less well defined. Here, we combined bioenergetic profiling and 13C-glucose infusion techniques to investigate the metabolism of CD8+ T cells responding to Listeria infection. In contrast to in vitro-activated T cells, which display hallmarks of Warburg metabolism, physiologically activated CD8+ T cells 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+ T cell expansion in vivo. Our data highlight fundamental differences in glucose use by pathogen-specific T cells in vivo, illustrating the impact of environment on T cell metabolic phenotypes. Although much is known about the metabolism of cultured T cells, how T cells use nutrients during immune responses in vivo is not well defined. Using 13C-glucose isotope tracing in mice, Ma et al. demonstrate prominent use of glucose for anabolic metabolism by T cells in vivo. This work highlights the importance of studying T cell metabolism in a physiological environment.

Original languageEnglish (US)
Pages (from-to)856-870.e5
JournalImmunity
Volume51
Issue number5
DOIs
StatePublished - Nov 19 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Ma, E. H., Verway, M. J., Johnson, R. M., Roy, D. G., Steadman, M., Hayes, S., Williams, K. S., Sheldon, R. D., Samborska, B., Kosinski, P. A., Kim, H., Griss, T., Faubert, B., Condotta, S. A., Krawczyk, C. M., DeBerardinis, R. J., Stewart, K. M., Richer, M. J., Chubukov, V., ... Jones, R. G. (2019). Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells. Immunity, 51(5), 856-870.e5. https://doi.org/10.1016/j.immuni.2019.09.003