Regulation of immunlity by a novel population of Qa-1-restricted CD8αα+TCRαβ+ T cells

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 alpha beta(+) Tregs that control activated V beta 8.2(+) CD4 T cells mediating experimental autoimmune encephalomyelitis. They express exclusively the CD8 alpha alpha homodimer and recognize a peptide from a conserved region of the TCR V beta 8.2 chain in the context of the Qa-1a (CD8 alpha alpha Tregs). They secrete type 1 cytokines but not IL-2. CD8 alpha alpha Tregs kill activated V beta 8.2(+) but not V beta 8.2(-) or naive T cells. The CD8 alpha alpha 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 Journal of Immunology, 2006, 177: 7645-7655.