Induction of regulatory T cells by the immunomodulating cytokines α-melanocyte-stimulating hormone and transforming growth factor-β2

Abstract

Recently, we have reported that the cytokines α-melanocyte-stimulating hormone (α-MSH) and transforming growth factor-β2 (TGF-β2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used α-MSH and TGF-β2 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 TGF-β1, and their production of interferon-γ, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that α-MSH with TGF-β2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immunomodulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress autoimmune disease.