Anti-TCR antibody treatment activates a novel population of nonintestinal CD8αα+TCRαβ+ regulatory T cells and prevents experimental autoimmune encephalomyelitis

CD8 alpha alpha(+)CD4(-)TCR alpha beta(+) 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 alpha alpha(+)CD4(-)TCR alpha beta(+) regulatory T cells (CD8 alpha alpha Tregs) that recognize a TCR peptide from the conserved CDR2 region of the TCR V beta 8.2-chain in the context of a class Ib molecule, Qa-1a, and control-activated V,beta 8.2(+) T cells mediating experimental autoimmune encephalomyelitis. Using flow cytometry, spectratyping, and realtime PCR analysis of T cell clones and short-term lines, we have determined the TCR repertoire of the CD8aa regulatory T cells (Tregs) and found that they predominantly use the TCR V beta 6 gene segment. In vivo injection of anti-TCR V beta 6 mAb results in activation of the CD8aa 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 CD8aa Tregs present in peripheral lymphoid organs other than the gut can be exploited for the control of T cell-mediated autoimmune diseases. The Journal of Immunology, 2007, 178: 6043-6050.