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- Title
Amelioration of arthritis through mobilization of peptide-specific CD8<sup>+</sup> regulatory T cells.
- Authors
Leavenworth, Jianmei W.; Xiaolei Tang; Kim, Hye-Jung; Xiaoyang Wang; Cantor, Harvey
- 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 autore-active T cells that initiate the disease cascade and break self tolerance. The murine MHC class lb molecule Qa-lb (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60p2i6 and Qdm. We found that peptide-induced expansion of tetramer-binding CD8+ Tregs that recognize Qa-1-Hsp60P216 but not Qa-l-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheu-matoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (TFH) and Thl7 cells by CD8+ Tregs inhibited disease development. Infusion of in vitro-expanded CD8+ Tregs increased the efficacy of meth-otrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-l-Hsp60p216-specific CD8+ Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60p216 peptide immuni-zation. These results suggest that strategies designed to expand Qa-1-restricted (HIA-E-restricted), peptide-specific CD8+ Tregs represent a promising therapeutic approach to autoimmune disorders.
- Publication
Journal of Clinical Investigation, 2013, Vol 123, Issue 3, p1382
- ISSN
0021-9738
- Publication type
Academic Journal
- DOI
10.1172/JCI66938