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

Abstract:

:Regulatory 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.

journal_name

Hum Vaccin Immunother

authors

Zhou X,Zhang S,Yu F,Zhao G,Geng S,Yu W,Wang XY,Wang B

doi

10.1080/21645515.2019.1616504

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

240-250

issue

2

eissn

2164-5515

issn

2164-554X

journal_volume

16

pub_type

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