Tolerogenic vaccine composited with islet-derived multipeptides and cyclosporin A induces pTreg and prevents Type 1 diabetes in murine model

Abstract

ABSTRACTRegulatory T cells (Tregs) play a crucial role in the control of the initiation and progression of type 1 diabetes (T1D). Various immunological interventions including those to ex vivo expansion Tregs transfer, in vivo induction of peripherally derived Treg (pTreg) have been considered as promising approaches for T1D therapy. In this study, we developed a novel tolerogenic vaccine using four autoantigenic peptides of islet-derived with cyclosporine A (CsA) as the pTreg inducer, designated as GAD-IN+CsA. This vaccine immunized into prediabetic NOD mice subcutaneously could induce IL-10 and TGF-β expressing pTregs and lead to suppressing autoreactive T cells responses, resulting in the prevention of T1D in these animals. Furthermore, we demonstrated that CsA with autoantigenic peptides modulates dendritic cells (DCs) to become immature IL-10hiCD40lo DCs. Such modulated DCs could foster naïve CD4+CD25− T cell into Tregs when presenting antigen peptides in vitro. This novel approach offers an alternative strategy to induce pTregs to treat T1D.