[en] Cytotoxic T lymphocytes (CTLs) are key players to eliminate tumorigenic or pathogen-infected cells using lytic granules (LG) and Fas ligand (FasL) pathways. Depletion of glucose leads to severely impaired cytotoxic function of CTLs. However, the impact of excessive glucose on CTL functions still remains largely unknown. Here we used primary human CD8+ T cells, which were stimulated by CD3/CD28 beads and cultured in medium either containing high glucose (HG, 25 mM) or normal glucose (NG, 5.6 mM). We found that in HG-CTLs, glucose uptake and glycolysis were enhanced, whereas proliferation remained unaltered. Furthermore, CTLs cultured in HG exhibited an enhanced CTL killing efficiency compared to their counterparts in NG. Unexpectedly, expression of cytotoxic proteins (perforin, granzyme A, granzyme B and FasL), LG release, cytokine/cytotoxic protein release and CTL migration remained unchanged in HG-cultured CTLs. Interestingly, additional extracellular Ca2+ diminished HG-enhanced CTL killing function. Our findings suggest that in an environment with excessive glucose, CTLs could eliminate target cells more efficiently, at least for a certain period of time, in a Ca2+-dependent manner.
Disciplines :
Immunology & infectious disease
Author, co-author :
Zhu, Jie; Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China ; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Yang, Wenjuan; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Zhou, Xiangda; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Zöphel, Dorina; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Soriano-Baguet, Leticia; Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Immunology and Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg ; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Dolgener, Denise; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Carlein, Christopher; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Hof, Chantal; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Zhao, Renping; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Ye, Shandong; Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
Schwarz, Eva C; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
BRENNER, Dirk ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics ; Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark
Prates Roma, Leticia; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Qu, Bin; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany ; INM - Leibniz Institute for New Materials, Saarbrücken, Germany
This project was funded by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 1027 project A2 to BQ, TRR219 (M04) to LP), INM Fellow, and HOMFOR2019 (to BQ) and Forschungsgroßgeräte (GZ: INST 256/423-1 FUGG and GZ: INST 256/419-1 FUGG) for flow cytometer and light-sheet microscope, respectively. LS-B and DB are funded by the FNR, respectively by the PRIDE (PRIDE/11012546/NEXTIMMUNE) and the ATTRACT program (A14/BM/7632103).We thank the Institute for Clinical Hemostaseology and Transfusion Medicine for providing donor blood; Annette Lis for mouse CD8+ T cell preparation and EG7-pCasper cells, Carmen H?ssig, Cora Hoxha and Gertrud Sch?fer for excellent technical help; Sandra Janku for her careful and critical reading; We are grateful to Markus Hoth for constant support, inspiring discussions and advice regarding writing of the manuscript. All the experiments except seahorse assay were conducted in Saarland University.
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