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Article
Nature Immunology  5, 818 - 827 (2004)
Published online: 18 July 2004; | doi:10.1038/ni1096

T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation

Sharon H Jackson1, 5, Satish Devadas2, 4, 5, Jaeyul Kwon2, 4, 5, Ligia A Pinto3 & Mark S Williams2, 4

1  Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

2  Department of Immunology, Holland Lab, American Red Cross, Rockville, Maryland 20855, USA.

3  Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.

4  Present addresses: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA (J.K. and M.S.W.) and Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA (S.D.).

5  These authors contributed equally to this work.

Correspondence should be addressed to Mark S Williams willmark@usa.redcross.org
T cell receptor (TCR) stimulation induces rapid generation of reactive oxygen species, although the mechanisms for this are unclear. Here we found that T cells expressed a functional phagocyte-type nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. TCR crosslinking induced oxidase activation through the recruitment of preformed Fas ligand and Fas. TCR stimulation induced three separable events generating reactive oxygen species: rapid hydrogen peroxide production independent of Fas or NADPH oxidase; sustained hydrogen peroxide production dependent on both Fas and NADPH oxidase; and delayed superoxide production that was dependent on Fas ligand and Fas yet independent of NADPH oxidase. NADPH oxidase−deficient T cells showed enhanced activation of the kinase Erk and a relative increase in T helper type 1 cytokine secretion. Thus, mature T cells express a phagocyte-type NADPH oxidase that regulates elements of TCR signaling.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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