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: Hsp60p216 and Qdm. We found that peptide-induced expansion of tetramer-binding CD8+ Tregs that recognize Qa-1–Hsp60p216 but not Qa-1–Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (TFH) and Th17 cells by CD8+ Tregs inhibited disease development. Infusion of in vitro–expanded CD8+ Tregs increased the efficacy of methotrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-1–Hsp60p216–specific CD8+ Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60p216 peptide immunization. These results suggest that strategies designed to expand Qa-1–restricted (HLA-E–restricted), peptide-specific CD8+ Tregs represent a promising therapeutic approach to autoimmune disorders.
Jianmei W. Leavenworth, Xiaolei Tang, Hye-Jung Kim, Xiaoyang Wang, Harvey Cantor
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at email@example.com.