Tolerogenic Vaccination Reduced Effector Memory CD4 T Cells and Induced Effector Memory Treg Cells for Type I Diabetes Treatment

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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Combination Therapy Using IL-2/IL-2 Monoclonal Antibody Complexes, Rapamycin, and Islet Autoantigen Peptides Increases Regulatory T Cell Frequency and Protects against Spontaneous and Induced Type 1 Diabetes in Nonobese Diabetic Mice

“…Because administration of peptide Ag together with immunomodulatory reagents favors the induction of Ag-specific Tregs in vivo (32,53,54), we assume it should be desirable to include islet Ag peptide in the combination, and indeed such a combination promoted significant Ag-specific Treg expansion in the spleens and pancreatic lymph nodes (Fig. 2B, 2C).…”

Two-dose seasonal influenza vaccine coverage and timeliness among children aged 6 months through 3 years: An evidence from the 2010–11 to the 2014–15 seasons in Zhejiang province, east China

“…Third, parents may not be able or willing to overcome barriers, like missing work or school, for their children's SIV. According to our previous study, 17 we assumed this phenomenon would be more significant among migrant children, whose parents had not enough time for primary healthcare and were less aware of the information on vaccination. Furthermore, the poorer education level of migrant parents would also influence their awareness and capacity to seek and take advantage of vaccination service and other public health service.…”