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(Journal of Leukocyte Biology. 2002;72:946-952.)
© 2002 by Society for Leukocyte Biology

Induction of regulatory T cells by the immunomodulating cytokines -melanocyte-stimulating hormone and transforming growth factor-ß2

Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts

Correspondence: Andrew W. Taylor, Ph.D., Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114. E-mail: awtaylor{at}vision.eri.harvard.edu

Recently, we have reported that the cytokines -melanocyte-stimulating hormone (-MSH) and transforming growth factor-ß2 (TGF-ß2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used -MSH and TGF-ß2 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-ß1, 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 TGF-ß2 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.

Key Words: regulatory T lymphocytes • regional immunity • immunosuppression

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