Microparticles Bearing Peptides Induce Antigen-specific Immunological Tolerance And The Effect In Type 1 Diabetes

Objective To study of microparticles bearing peptides induce antigen-specific immunological tolerance and the effect and significance in T1DM.Methods The zinc transporter 8(ZnT8)-3,6 and 9 antigen epitope peptides were subcutaneous injected into HLA-A2.1 transgenic mice respectively, then the change of regulatory T cells, CD4+ and CD8+T cells and antigen specific CD8+ T cells were observed. And after the cell suspension of HLA-A2.1 transgenic mice and type 1 diabetes were co-cultured with ZnT8-polystyrene beads(PSB) or cytomegalovirus (CMV)-PSB, the change of antigen specific T cells were observed.Results The proportion of Treg was significantly higher in groups immunized with ZnT8-3,6 and 9 antigen epitope peptides than blank control groups(p=0.001, p=0.0007 and p=0.0005 respectively). Compared with CMV antigen specific CD8+ T cells, groups immunized with ZnT8-3,6 and 9 antigen epitope peptides had significantly higher proportion of ZnT8 antigen specific CD8+ T cells(p=0.0124, p=0.0245 and p=0.0268, respectively). Compared with groups cultured CMV-PSB, groups cultured with ZnT8-PSB had significantly lower proportion of antigen specific T cells after HLA-A2.1 transgenic mice were immunized with ZnT8-3,6 and 9 antigen epitope peptides respectively (p=0.0209, p=0.0066 and p=0.0160, respectively). The proportion of antigen specific CD8+T cells was significantly lower in groups cultured with ZnT8-PSB than groups cultured CMV-PSB in patients with T1DM.Conclusions All three antigen epitope peptides of ZnT8 could produce antigen specific CD8+ T cells in HLA-A2.1 transgenic mice. After co-cultured with ZnT8-PSB, the proportion of antigen specific CD8+ T cells was reduced in HLA-A2.1 transgenic mice, and also reduced in patients with T1DM. The mechanism need to be further researched.