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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901533v1 183/7/4675    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Crispín, J. C. Articles by Tsokos, G. C. PubMed PubMed Citation Articles by Crispín, J. C. Articles by Tsokos, G. C.

Human TCR-β⁺ CD4^– CD8^– T Cells Can Derive from CD8⁺ T Cells and Display an Inflammatory Effector Phenotype¹

Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115

The origin and function of human double negative (DN) TCR-β⁺ T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. In this study, we provide evidence that human TCR-β⁺ CD4^– CD8^– DN T cells can derive from activated CD8⁺ T cells. Freshly isolated TCR-β⁺ DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8⁺ T cells produce a defined array of proinflammatory mediators that includes IL-1β, IL-17, IFN-, CXCL3, and CXCL2. These results indicate that, upon activation, CD8⁺ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity.

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 R01 AI42269 and R01 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: DN, double negative; SLE, systemic lupus erythematosus; FasL, Fas ligand; PI, propidium iodide.

⁴ The online version of this article contains supplementary material.