Cited by 459Redox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative MechanismsT-cell and B-cell Immunology

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Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation

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Devadas, Satish, Zaritskaya, Luba, Rhee, Sue Goo, Oberley, Larry, Williams, Mark S.·2002·The Journal of Experimental Medicine

DOI 10.1084/jem.20010659PMC PMC2196010

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Abstract

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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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)
ORCID: Devadas, Satish
Rhee, Sue Goo
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
DOI: 10.1084/jem.20010659
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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Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation

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