Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity.

Regulatory T (Treg) cells help to maintain tolerance and prevent the development of autoimmune diseases. Retinoic acid (RA) can promote peripheral conversion of na?ve T cells into Foxp3 Treg cells. Here， we show that RA can act as an adjuvant to induce antigen-specific type 1 Treg (Tr1) cells， which is augmented by co-administration of IL-2. Immunization of mice with the model antigen KLH in the presence of RA and IL-2 induces T cells that secrete IL-10， but not IL-17 or IFN-γ， and express LAG-3， CD49b and PD-1 but not Foxp3， a phenotype typical of Tr1 cells. Furthermore， immunization of mice with the autoantigen MOG in the presence of RA and IL-2 induces Tr1 cells， which suppress pathogenic Th1 and Th17 cells that mediate the development of experimental autoimmune encephalomyelitis (EAE)， an autoimmune disease of the CNS. Furthermore， immunization with a surrogate autoantigen， RA and IL-2 prevents development of spontaneous autoimmune uveitis. Our findings demonstrate that the induction of autoantigen-specific Tr1 cells can prevent the development of autoimmunity.