Tolerogenic Vaccination Reduced Effector Memory CD4 T Cells and Induced Effector Memory Treg Cells for Type I Diabetes Treatment |
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| Authors: | Jingyao Zhang Wenjuan Gao Xu Yang Jingjing Kang Yongliang Zhang Qirui Guo Yanxin Hu Guoliang Xia Youmin Kang |
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| Affiliation: | 1. State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.; 2. Department of Modern Sciences & Technology, Agricultural University of Hebei, Baoding, China.; 3. College of Veterinary Medicine, China Agricultural University, Beijing, China.; McGill University Health Center, Canada, |
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| Abstract: | BackgroundVaccination could induce immune tolerance and protected NOD mice from the development of type I diabetes (T1D). We previously demonstrated that insulin peptide (B9-23) combined with dexamethasone (DEX) stimulated the expansion of antigen specific regulatory T (Treg) cells which in turn effectively prevented T1D in NOD mice. Here, we aimed to investigate the therapeutic effect of tolerogenic vaccination for T1D treatment.Methodology/Principal FindingsThe diabetic NOD mice (Blood glucose level ≧250 mg/dl) were treated with B9-23 and DEX twice. The tolerance was restored by blocking maturation of dendritic cells (DCs) and inducing Treg cells in treated NOD mice. Remarkably, the reduction of autoreactive effector memory CD4 T (Tm) cells and the induction of functional effector memory Treg (mTreg) cells contributed to the improvement of T1D in treated NOD mice.Conclusions/SignificanceTolerogenic vaccination restored tolerance and ameliorated T1D by suppressing effector CD4 Tm cells and inducing effector mTreg cells. Our findings implicate the potential of tolerogenic vaccination for T1D treatment. |
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