TY - JOUR
T1 - Memory CD8+ T cells upregulate glycolysis and effector functions under limiting oxygen conditions
AU - Beumer-Chuwonpad, Ammarina
AU - van Alphen, Floris P. J.
AU - Kragten, Natasja A. M.
AU - Freen-van Heeren, Julian J.
AU - Rodriguez Gomez, Maria
AU - Verhoeven, Arthur J.
AU - van den Biggelaar, Maartje
AU - van Gisbergen, Klaas P. J. M.
N1 - Funding Information: The authors thank Mark Hoogenboezem, Simon Tol, and Erik Mul (Sanquin Central Facility) for technical support regarding to cell sorting, Mark Hoogenboezem for technical support regarding to mouse experiments and Lodewijk IJlst and Riekelt Houtkooper (Amsterdam UMC) for their technical support regarding to the Seahorse metabolic assays. Lastly, the authors also thank Ramon Arens (LUMC) for kindly providing SIINFEKLH-2Kb MHC tetramers, Brian Sheridan (Stony Brook University) for kindly providing Lm-OVA (InlAM strain 10403s) and Emile van den Akker and Marten Hansen (Sanquin Research) for generously providing culture media. A.B.C. and K.P.J.M.v.G were supported by Vici fellowship 09150182110031 from The Netherlands Organisation for Health Research and Development (NWO-ZonMw). Funding Information: The authors thank Mark Hoogenboezem, Simon Tol, and Erik Mul (Sanquin Central Facility) for technical support regarding to cell sorting, Mark Hoogenboezem for technical support regarding to mouse experiments and Lodewijk IJlst and Riekelt Houtkooper (Amsterdam UMC) for their technical support regarding to the Seahorse metabolic assays. Lastly, the authors also thank Ramon Arens (LUMC) for kindly providing SIINFEKL MHC tetramers, Brian Sheridan (Stony Brook University) for kindly providing ‐OVA (InlA strain 10403s) and Emile van den Akker and Marten Hansen (Sanquin Research) for generously providing culture media. A.B.C. and K.P.J.M.v.G were supported by Vici fellowship 09150182110031 from The Netherlands Organisation for Health Research and Development (NWO‐ZonMw). H‐2Kb Lm M Publisher Copyright: © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2023/2
Y1 - 2023/2
N2 - Memory CD8+ T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence at oxygen-deprived infected tissue sites or in tumors, the impact of local oxygen pressure on memory CD8+ T cells remains largely unclear. We sought to elucidate how oxygen pressure impacts memory CD8+ T cells arising after infection with Listeria monocytogenes-OVA. Our data revealed that reduced oxygen pressure during in vitro culture switched CD8+ T cell metabolism from oxidative phosphorylation to a glycolytic phenotype. Quantitative proteomic analysis showed that limiting oxygen conditions increased the expression of glucose transporters and components of the glycolytic pathway, while decreasing TCA cycle and mitochondrial respiratory chain proteins. The altered CD8+ T cell metabolism did not affect the expansion potential, but enhanced the granzyme B and IFN-γ production capacity. In vivo, memory CD8+ T cells cultured under low oxygen pressure provided protection against bacterial rechallenge. Taken together, our study indicates that strategies of cellular immune therapy may benefit from reducing oxygen during culture to develop memory CD8+ T cells with superior effector functions.
AB - Memory CD8+ T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence at oxygen-deprived infected tissue sites or in tumors, the impact of local oxygen pressure on memory CD8+ T cells remains largely unclear. We sought to elucidate how oxygen pressure impacts memory CD8+ T cells arising after infection with Listeria monocytogenes-OVA. Our data revealed that reduced oxygen pressure during in vitro culture switched CD8+ T cell metabolism from oxidative phosphorylation to a glycolytic phenotype. Quantitative proteomic analysis showed that limiting oxygen conditions increased the expression of glucose transporters and components of the glycolytic pathway, while decreasing TCA cycle and mitochondrial respiratory chain proteins. The altered CD8+ T cell metabolism did not affect the expansion potential, but enhanced the granzyme B and IFN-γ production capacity. In vivo, memory CD8+ T cells cultured under low oxygen pressure provided protection against bacterial rechallenge. Taken together, our study indicates that strategies of cellular immune therapy may benefit from reducing oxygen during culture to develop memory CD8+ T cells with superior effector functions.
KW - CD8 memory T cells
KW - Cytotoxic T cells
KW - Hypoxic T cell cultures
KW - T cell metabolism
KW - glycolysis
UR - http://www.scopus.com/inward/record.url?scp=85144065827&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.202249918
DO - https://doi.org/10.1002/eji.202249918
M3 - Article
C2 - 36482267
SN - 0014-2980
VL - 53
JO - European journal of immunology
JF - European journal of immunology
IS - 2
M1 - 2249918
ER -