Regulatory T cells control diabetes without compromising acute anti-viral defense

调节性T细胞控制糖尿病而不损害急性抗病毒防御

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作者:Carmen Baca Jones #, Philippe P Pagni #, Georgia Fousteri #, Sowbarnika Sachithanantham, Amy Dave, Teresa Rodriguez-Calvo, Jacqueline Miller, Matthias von Herrath

Abstract

While previous reports have demonstrated the efficacy of regulatory T cell therapy in the prevention of diabetes, systemic immunocompromise and Treg instability remain key safety concerns. Here we examined the influence of induced Treg (iTreg) cell therapy on anti-viral host defense and autoimmune T cell responses during acute viral infection in a murine model of autoimmune diabetes. Protective transfers of iTregs maintained IL-10 expression, expanded in vivo and controlled diabetes, despite losing FoxP3 expression. Adoptive transfer of iTregs affected neither the primary anti-viral CD8 T cell response nor viral clearance, although a significant and sustained suppression of CD4 T cell responses was observed. Following acute viral clearance, iTregs transferred early suppressed both CD4 and CD8 T cell responses, which resulted in the reversion of diabetes. These observations indicate that iTregs suppress local autoimmune processes while preserving the immunocompetent host's ability to combat acute viral infection.

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