H uman CD4+ T cells maintain specific functions even under conditions of extremely restricted ATP production
Open accessAbstract
We investigated the energy‐adaptive potential of human CD4+ T cells under conditions of impaired oxidative phosphorylation (OXPHOS) and/or low glucose (inhibiting glycolysis). These cells often encounter these conditions when executing their functions in injured/inflamed tissues, even though T cells themselves require constant and adequate energy supply via ATP. We assessed two specific functions, cytokine synthesis and proliferation, and addressed whether adaptive characteristics also emerged in vivo. In glucose‐containing medium, both cytokine production and proliferation were unaffected, even under complete OXPHOS suppression. Only when glucose was also absent were these functions significantly decreased. Partial recovery of OXPHOS and induced glycolysis were crucial for the maintenance of cellular energy supply. Adaptive regulatory mechanisms are clinically relevant because hypoxia up‐regulates glycolytic genes but down‐regulates OXPHOS genes in vivo. Our data demonstrate an unexpectedly high, clinically relevant adaptive potential of human CD4+ T cells to maintain specific functions even under severely impaired bioenergetic conditions. Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/200838047_s.pdf
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T cells activated at physiologic O2 tension (2-5% O2) have reduced proliferation and expansion following TCR stimulation.
“when T cells are activated in conditions of physiologic oxygen tension (2–5 % O2, ~2–5 kPa, or ~15–38 mm Hg), there are a number of changes in T cell dynamics. First, T cells activated at physiologic O2 tension have reduced proliferation and expansion following TCR stimulation.”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [73]
T cells are able to preserve functionalities including cytokine production even in conditions of severe metabolite restriction including limited oxygen glucose.
“T cells are able to preserve functionalities including cytokine production even in conditions of severe metabolite restriction including limited oxygen glucose [73].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [73]
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Self-citation
- Authors
- Tripmacher, R., Gaber, T., Dziurla, R., Häupl, T., Erekul, K., Grützkau, A., Tschirschmann, M., Scheffold, A., Radbruch, A., Burmester, G., & Buttgereit, F.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- German Rheumatism Research Centre (DE)
- Corresponding author
- Buttgereit, Frank
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2008-05-20
- Volume
- 38
- Issue
- 6
- Pages
- 1631-1642
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2016562301
- Cited by
- 46
- References
- 41
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GS0413, 01GS0160, 01GS0110, 01GS0110/01GS0160/01GS0413)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- CD4+ T cells, oxidative phosphorylation, glycolysis, glucose deprivation, hypoxia, ATP production, cytokine production, T cell proliferation, inflammation
- MeSH terms
- Adenosine Triphosphate, Hypoxia, Arthritis, Rheumatoid, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Glucose, Glycolysis, Humans, Lymphocyte Activation, Methacrylates, Osteoarthritis, Oxidative Phosphorylation, Oxygen Consumption, Tetradecanoylphorbol Acetate, Thiazoles, Electron Transport Complex III, CD4-Positive T-Lymphocytes, Ionomycin, Gene Expression, Cytokines, Joint Capsule, Gene Expression Profiling, Cytochromes b, Cell Proliferation
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