Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells.

ABSTRACT: Current therapies to treat autoimmune disease focus mainly on downstream targets of autoimmune responses, including effector cells and cytokines. A potentially more effective approach would entail targeting autoreactive T cells that initiate the disease cascade and break self tolerance. The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60(p216) and Qdm. We found that peptide-induced expansion of tetramer-binding CD8(+) Tregs that recognize Qa-1-Hsp60(p216) but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (T(FH)) and Th17 cells by CD8(+) Tregs inhibited disease development. Infusion of in vi

SUBMITTER: Leavenworth JW 

PROVIDER: S-EPMC3582146 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature