@article{43c050461434400287bb531e5bf25264,
title = "Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells",
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.",
author = "Ma, {Eric H.} and Verway, {Mark J.} and Johnson, {Radia M.} and Roy, {Dominic G.} and Mya Steadman and Sebastian Hayes and Williams, {Kelsey S.} and Sheldon, {Ryan D.} and Bozena Samborska and Kosinski, {Penelope A.} and Hyeryun Kim and Takla Griss and Brandon Faubert and Condotta, {Stephanie A.} and Krawczyk, {Connie M.} and DeBerardinis, {Ralph J.} and Stewart, {Kelly M.} and Richer, {Martin J.} and Victor Chubukov and Roddy, {Thomas P.} and Jones, {Russell G.}",
note = "Funding Information: We thank Shona Mookerjee; members of the Jones, Krawczyk, and Richer laboratories; and colleagues at Agios Pharmaceuticals for advice regarding the manuscript. We acknowledge technical assistance from Jeanie Wedberg, Michelle Minard, VAI Operations, and the Metabolomics and Flow Cytometry Core facilities at the VAI and McGill/GCRC . The GCRC Metabolomics Core Facility is supported by grants from the Canadian Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), and Terry Fox Research Institute (TFRI). We acknowledge salary support from the McGill Integrated Cancer Research Training Program (to E.H.M.), Fonds de la Recherche du Qu{\'e}bec – Sant{\'e} (FRQS; to E.H.M., D.G.R., and M.J.R.), and the CIHR (to D.G.R. and R.G.J.). This research was supported by grants from the CIHR (including MOP-142259 to R.G.J.) and funding from Agios Pharmaceuticals . Funding Information: We thank Shona Mookerjee; members of the Jones, Krawczyk, and Richer laboratories; and colleagues at Agios Pharmaceuticals for advice regarding the manuscript. We acknowledge technical assistance from Jeanie Wedberg, Michelle Minard, VAI Operations, and the Metabolomics and Flow Cytometry Core facilities at the VAI and McGill/GCRC. The GCRC Metabolomics Core Facility is supported by grants from the Canadian Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), and Terry Fox Research Institute (TFRI). We acknowledge salary support from the McGill Integrated Cancer Research Training Program (to E.H.M.), Fonds de la Recherche du Qu?bec ? Sant? (FRQS; to E.H.M. D.G.R. and M.J.R.), and the CIHR (to D.G.R. and R.G.J.). This research was supported by grants from the CIHR (including MOP-142259 to R.G.J.) and funding from Agios Pharmaceuticals. Experimental design and execution was conducted by E.H.M. M.J.V. D.G.R. M.S. S.H. B.S. P.A.K. H.K. S.A.C. C.M.K. M.J.R. K.M.S. T.P.R. and R.G.J. Bioinformatics and data analysis was conducted by E.H.M. R.M.J. R.D.S. and V.C. Data interpretation was performed by E.H.M. M.S. B.F. T.G. R.J.D. V.C. T.P.R. and R.G.J. The manuscript was written and edited by E.H.M. K.S.W. and R.G.J. S.H. P.A.K. H.K. K.M.S. V.C. and T.P.R. are employees and shareholders of Agios Pharmaceuticals. R.G.J. is a consultant to Agios Pharmaceuticals and is a shareholder and member of the scientific advisory board of Immunomet Therapeutics. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = nov,
day = "19",
doi = "10.1016/j.immuni.2019.09.003",
language = "English (US)",
volume = "51",
pages = "856--870.e5",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}