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Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation
Open accessAbstract
Receptor-stimulated generation of reactive oxygen species (ROS) has been shown to regulate signal transduction, and previous studies have suggested that T cell receptor (TCR) signals may involve or be sensitive to ROS. In this study, we have shown for the first time that TCR cross-linking induced rapid (within 15 min) generation of both hydrogen peroxide and superoxide anion, as defined with oxidation-sensitive dyes, selective pharmacologic antioxidants, and overexpression of specific antioxidant enzymes. Furthermore, the data suggest the novel observation that superoxide anion and hydrogen peroxide are produced separately by distinct TCR-stimulated pathways. Unexpectedly, TCR-stimulated activation of the Fas ligand (FasL) promoter and subsequent cell death was dependent upon superoxide anion, but independent of hydrogen peroxide, while nuclear factor of activated T cells (NFAT) activation or interleukin 2 transcription was independent of all ROS. Anti-CD3 induced phosphorylation of extracellular signal–regulated kinase (ERK)1/2 required hydrogen peroxide generation but was unaffected by superoxide anion. Thus, antigen receptor signaling induces generation of discrete species of oxidants that selectively regulate two distinct redox sensitive pathways, a proapoptotic (FasL) and a proliferative pathway (ERK).
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“There has long been evidence that ROS can play critical roles in shaping T cell responses (28–30).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [29]
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Metadata
- Authors
- Devadas, S., Zaritskaya, L., Rhee, S. G., Oberley, L., & Williams, M. S.
- Affiliations
- American Red Cross (US)
- National Institutes of Health (US)
- University of Iowa (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-01-07
- Volume
- 195
- Issue
- 1
- Pages
- 59-70
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2196010
- OpenAlex
- W2157579772
- Cited by
- 458
- References
- 59
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 22 · 2023: 10 · 2022: 19 · 2021: 26 · 2020: 29 · 2019: 19 · 2018: 18 · 2017: 21 · 2016: 19 · 2015: 19 · 2014: 21 · 2013: 18 · 2012: 15
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- T cell receptor signaling, reactive oxygen species, superoxide, hydrogen peroxide, T cell activation, apoptosis, NFAT activation, interleukin-2 transcription, ERK1/2 phosphorylation, redox signaling, oxidative stress
- MeSH terms
- Animals, Humans, Hybridomas, Hydrogen Peroxide, Lymphocyte Activation, Membrane Glycoproteins, Oxidation-Reduction, Peroxides, Receptors, Antigen, T-Cell, Superoxides, T-Lymphocytes, Signal Transduction, Free Radical Scavengers, Apoptosis, CD3 Complex, Reactive Oxygen Species, Models, Immunological, Mitogen-Activated Protein Kinases, Mice, Fas Ligand Protein
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