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Holthaus, L. ; Sharma, V. ; Brandt, D. ; Ziegler, A.-G. ; Jastroch, M. ; Bonifacio, E.

Functional and metabolic fitness of human CD4+ T lymphocytes during metabolic stress.

Life Sci. All. 4:e202101013 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T-cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, whereas early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T-cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T-cell proliferation, but not T-cell activation. Conditions that inhibited T-cell activation were associated with the down-regulation of 2',5'-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T-cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress, and/or the function of T cells in these conditions will improve the efficacy of T-cell-based therapies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Journal Life Science Alliance
Quellenangaben Volume: 4, Issue: 12, Pages: , Article Number: e202101013 Supplement: ,
Publisher EMBO Press
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)
Institute of Diabetes and Obesity (IDO)