A novel mimovirus encoding ChgA10-19 peptide with PD-L1 induces T cell tolerance and ameliorates the severity of diabetes

Abstract

Related studies demonstrate that type 1 diabetes (T1D) is caused by β-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA_10-19 peptide with PD-L1 was constructed. The NOD.β2m null HHD mice were administrated with mimovirus transduced DCs. After immunization, the activation and proliferation of CD8+ T cells were detected, diabetes incidence and pancreatic tissue destruction were also analyzed. The results demonstrated that transduced DCs attenuated CD8+ T cell activation and proliferation. In addition, transduced DCs inhibited CD8+ T response to ChgA stimulation, and ameliorated the severity of diabetes. These data suggested that mimovirus transduced DCs might provide novel clues for T1D therapy.

Keywords: Chg(A10–19); Diabetes; Mimovirus; PD-L1; T cell tolerance.