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

Nature Immunology volume 5, pages 818–827 (2004)Cite this article

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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Figure 1: Anti-CD3-stimulated generation of ROS in primary T blasts from C57BL/6 or p47phox-deficient mice.
Figure 2: Anti-CD3-stimulated generation of ROS in wild-type and oxidase-deficient T blasts: short-term kinetics.
Figure 3: Purified T cells express p47phox and p67phox.
Figure 4: T cells express an epitope recognized by 7D5 (anti-gp91phox).
Figure 5: Effect of DPI on anti-CD3-stimulated generation of ROS in wild-type and p47phox-deficient T blasts.
Figure 6: Effect of Fas-Ig on anti-CD3-stimulated generation of ROS in wild-type, p47phox-deficient or gp91phox-deficient T blasts.
Figure 7: Anti-CD3-induced MEK-Erk phosphorylation is selectively enhanced and/or sustained in T blasts in conditions in which hydrogen peroxide production is deficient.
Figure 8: Altered cytokine production in T cell blasts from gp91phox-deficient mice.

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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.

Author information

Author notes

  1. Jaeyul Kwon & Mark S Williams

    Present address: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA

  2. Satish Devadas

    Present address: Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA

  3. Sharon H Jackson, Satish Devadas and Jaeyul Kwon: These authors contributed equally to this work.

Authors and Affiliations

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

    Sharon H Jackson

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

    Satish Devadas, Jaeyul Kwon & Mark S Williams

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

    Ligia A Pinto

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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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