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Regulation of Immunity by a Novel Population of Qa-1-Restricted CD8⁺TCR⁺ T Cells¹

Xiaolei Tang^*, Igor Maricic^*, Nikunj Purohit^*, Berge Bakamjian^*, Lisa M. Reed-Loisel, Tara Beeston^*, Peter Jensen and Vipin Kumar^2,*

^* Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121; and Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132

Regulatory mechanisms involving CD8⁺ T cells (CD8 regulatory T cells (Tregs)) are important in the maintenance of immune homeostasis. However, the inability to generate functional CD8 Treg clones with defined Ag specificity has precluded a direct demonstration of CD8 Treg-mediated regulation. In the present study, we describe the isolation of functional lines and clones representing a novel population of TCR⁺ Tregs that control activated V8.2⁺ CD4 T cells mediating experimental autoimmune encephalomyelitis. They express exclusively the CD8 homodimer and recognize a peptide from a conserved region of the TCR V8.2 chain in the context of the Qa-1a (CD8 Tregs). They secrete type 1 cytokines but not IL-2. CD8 Tregs kill activated V8.2⁺ but not V8.2^– or naive T cells. The CD8 Tregs prevent autoimmunity upon adoptive transfer or following in vivo activation. These findings reveal an important negative feedback regulatory mechanism targeting activated T cells and have implications in the development of therapeutic strategies for autoimmune diseases and transplantation.

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: Treg, regulatory T cell; TCV, T cell vaccination; MBP, myelin basic protein; EAE, experimental autoimmune encephalomyelitis; ₂m, ₂-microglobulin; Tg, transgenic; PT, Pertussis toxin; TL, thymic leukemia; TAP, transporter associated with Ag processing; IEL, intraepithelial lymphocyte.

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