Anti-IL-7 receptor-[alpha] reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Genetic variation in the IL-7 receptor-... (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Rα antibody therapy reduces, the IFN-...-producing CD4+ (T...1) and IFN-...-producing CD8+ T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the inhibitory receptor Programmed Death 1 (PD-1) expression in the effector T cells. Programmed Death 1 blockade reversed the immune tolerance mediated by the IL-7R... antibody therapy. Furthermore, IL-7Rα antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7R... antibody therapy suggest a unique disease-modifying approach to T1D. (ProQuest: ... denotes formulae/symbols omitted.)