Memory CD8+ T cells upregulate glycolysis and effector functions under limiting oxygen conditions. Issue 2 (8th December 2022)

• Record Type: Journal Article
• Authors: Beumer‐Chuwonpad, Ammarina; van Alphen, Floris P.J.; Kragten, Natasja A.M.; Freen‐van Heeren, Julian J.; Rodriguez Gomez, Maria; Verhoeven, Arthur J.; van den Biggelaar, Maartje; van Gisbergen, Klaas P.J.M.
• Is Part Of: European journal of immunology. Volume 53:Issue 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-08
• Subjects: CD8+ memory T cells -- Cytotoxic T cells -- T cell metabolism -- Hypoxic T cell cultures -- glycolysis; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202249918
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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 i n 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. Abstract : Memory CD8 + T cells are rewired compared to naïve CD8 + T cells to provide improved protection against reinfection. We have analyzed the impact of oxygen availability on the effector function, metabolism, protein profile, and protective capacity of memory CD8 + T cells. Our results provide insight into oxygen‐dependent aspects of memory CD8 + T cell responses.