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Anti-TCR Antibody Treatment Activates a Novel Population of Nonintestinal CD8⁺TCR⁺ Regulatory T Cells and Prevents Experimental Autoimmune Encephalomyelitis¹

Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121

CD8⁺CD4^–TCR⁺ T cells are a special lineage of T cells found predominantly within the intestine as intraepithelial lymphocytes and have been shown to be involved in the maintenance of immune homeostasis. Although these cells are independent of classical MHC class I (class Ia) molecules, their origin and function in peripheral lymphoid tissues are unknown. We have recently identified a novel subset of nonintestinal CD8⁺CD4^–TCR⁺ regulatory T cells (CD8 Tregs) that recognize a TCR peptide from the conserved CDR2 region of the TCR V8.2-chain in the context of a class Ib molecule, Qa-1a, and control- activated V8.2⁺ T cells mediating experimental autoimmune encephalomyelitis. Using flow cytometry, spectratyping, and real-time PCR analysis of T cell clones and short-term lines, we have determined the TCR repertoire of the CD8 regulatory T cells (Tregs) and found that they predominantly use the TCR V6 gene segment. In vivo injection of anti-TCR V6 mAb results in activation of the CD8 Tregs, inhibition of the Th1-like pathogenic response to the immunizing Ag, and protection from experimental autoimmune encephalomyelitis. These data suggest that activation of the CD8 Tregs present in peripheral lymphoid organs other than the gut can be exploited for the control of T cell-mediated autoimmune diseases.

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 grants from the National Institutes of Health, National Multiple Sclerosis Society, Alzheimer’s and Aging Research Center, and Multiple Sclerosis National Research Institute (to V.K.).

² Address correspondence and reprint requests to Dr. Vipin Kumar, Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121. E-mail address: vkumar{at}tpims.org

³ Abbreviations used in this paper: iIEL, intestine intraepithelial lymphocyte; EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; PT, pertussis toxin; TL, thymic leukemia Ag; Treg, regulatory T cell.

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