Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2.
Recently, we have reported that the cytokines alpha-melanocyte-stimulating hormone (alpha-MSH) and transforming growth factor-beta2 (TGF-beta2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used alpha-MSH and TGF-beta2 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-beta1, and their production of interferon-gamma, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that alpha-MSH with TGF-beta2 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.
Namba
Kenichi
K
Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Kitaichi
Nobuyoshi
N
Nishida
Tomomi
T
Taylor
Andrew W
AW
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D005128:Eye Diseases / Q000276:immunology*; D005136:Eye Proteins; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D012173:Retinitis / Q000175:diagnosis / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D014605:Uveitis / Q000175:diagnosis / Q000276:immunology; D000521:alpha-MSH / Q000494:pharmacology*; D000099214:Retinol-Binding Proteins, Interstitial
D001324:Autoantigens; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D008222:Lymphokines; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D000521:alpha-MSH; D000099214:Retinol-Binding Proteins, Interstitial; C508961:Tgfb1 protein, mouse