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The Journal of Immunology, 2008, 181, 8761-8766
Copyright © 2008 by The American Association of Immunologists, Inc.

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Expanded Double Negative T Cells in Patients with Systemic Lupus Erythematosus Produce IL-17 and Infiltrate the Kidneys1

José C. Crispín*, Mohamed Oukka{dagger}, George Bayliss*, Robert A. Cohen*, Christine A. Van Beek{ddagger}, Isaac E. Stillman{ddagger}, Vasileios C. Kyttaris*, Yuang-Taung Juang* and George C. Tsokos2,*

* Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; {dagger} Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139; and {ddagger} Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02115

Double negative (DN) T cells are expanded in patients with systemic lupus erythematosus (SLE) and stimulate autoantibody production as efficiently as CD4+ T cells. In this study, we demonstrate that DN T cells from patients with SLE produce significant amounts of IL-17 and IFN-{gamma}, and expand when stimulated in vitro with an anti-CD3 Ab in the presence of accessory cells. Furthermore, IL-17+ and DN T cells are found in kidney biopsies of patients with lupus nephritis. Our findings establish that DN T cells produce the inflammatory cytokines IL-17 and IFN-{gamma}, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institutes of Health Grants RO1 AI42269 and RO1 AI49954 and by the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery funded by Rheuminations.

2 Address correspondence and reprint requests to Dr. George C. Tsokos, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS-937, Boston, MA 02115. E-mail address: gtsokos{at}bidmc.harvard.edu

3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; DN, double negative; DAPI, 4',6-diamidino-2-phenylindole.




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