Abstract
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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Acknowledgements
We thank P. Henkart and D. Scott for critical reading of the manuscript. Supported by the American Heart Association (0030033N) and American Red Cross.
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Supplementary information
Supplementary Fig. 1
Effect of an inhibitor of nitric oxide synthase (L-NMMA) on TCR stimulated ROS generation. (PDF 40 kb)
Supplementary Fig. 2
DCFDA and DHE oxidation occurs in T cells. (PDF 67 kb)
Supplementary Fig. 3
Purity of T cell blast preparations. (PDF 114 kb)
Supplementary Fig. 4
Specific expression of NADPH oxidase component message by murine CD4+ T cell blasts. (PDF 79 kb)
Supplementary Fig. 5
Role of FasL-Fas interactions in anti-CD3 stimulated generation of reactive oxygen species in human T blasts. (PDF 45 kb)
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Jackson, S., Devadas, S., Kwon, J. et al. T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat Immunol 5, 818–827 (2004). https://doi.org/10.1038/ni1096
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DOI: https://doi.org/10.1038/ni1096
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