Recently, we have reported that the cytokines -melanocyte-stimulating hormone ( -MSH) and transforming growth factor2 (TGF2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used -MSH and TGF2 to generate ocular autoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF1, and their production of interferon, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that -MSH with TGF2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immunomodulating cytokines to purposely induce antigenspecific Treg cells to prevent and suppress autoimmune disease. J. Leukoc. Biol. 72: 946–952; 2002.