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

First Author  Ma EH Year  2024
Journal  Sci Adv Volume  10
Issue  22 Pages  eadj1431
PubMed ID  38809979 Mgi Jnum  J:352025
Mgi Id  MGI:7644801 Doi  10.1126/sciadv.adj1431
Citation  Ma EH, et al. (2024) (13)C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. Sci Adv 10(22):eadj1431
abstractText  Infusion of (13)C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of (13)C-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.
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