Back to Search Start Over

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

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.
Source :
Science Advances. 5/31/2024, Vol. 10 Issue 22, p1-17. 17p.
Publication Year :
2024

Abstract

Infusion of 13C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of 13C-labeled metabolites (glucose, glutamine, and acetate) in Listeria monocytogenes-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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
23752548
Volume :
10
Issue :
22
Database :
Academic Search Index
Journal :
Science Advances
Publication Type :
Academic Journal
Accession number :
177552918
Full Text :
https://doi.org/10.1126/sciadv.adj1431