13 C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells

Infusion of C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of C-labeled metabolites (glucose, glutamine, and acetate) in -infected mice, we demonstrate that CD8 T effector (Teff) cells use met...

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Published inScience advances Vol. 10; no. 22; p. eadj1431
Main Authors Ma, Eric H, Dahabieh, Michael S, DeCamp, Lisa M, Kaymak, Irem, Kitchen-Goosen, Susan M, Oswald, Brandon M, Longo, Joseph, Roy, Dominic G, Verway, Mark J, Johnson, Radia M, Samborska, Bozena, Duimstra, Lauren R, Scullion, Catherine A, Steadman, Mya, Vos, Matthew, Roddy, Thomas P, Krawczyk, Connie M, Williams, Kelsey S, Sheldon, Ryan D, Jones, Russell G
Format Journal Article
LanguageEnglish
Published United States 31.05.2024
Subjects
Acetates - metabolism
Animals
Carbon Isotopes
CD8-Positive T-Lymphocytes - metabolism
Citric Acid Cycle
Glucose - metabolism
Glutamine - metabolism
Listeria monocytogenes
Listeriosis - immunology
Listeriosis - metabolism
Listeriosis - microbiology
Mice
Mice, Inbred C57BL
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Summary:Infusion of C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of C-labeled metabolites (glucose, glutamine, and acetate) in -infected mice, we demonstrate that CD8 T effector (Teff) cells use metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily toward nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support adenosine triphosphate and de novo pyrimidine synthesis. In addition, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)-which regulates de novo aspartate synthesis-for effector cell expansion in vivo. CD8 Teff cells change fuel preference over the course of infection, switching from glutamine- to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with CD8 Teff cell function in vivo.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adj1431