The Role of Beta Cell Antigen Presentation in Dendritic Cell-Based Type 1 Diabetes Immunotherapy (B189)

Dendritic cells (DCs) are promising cells for type 1 diabetes (T1D) immunotherapy. Most studies have been focusing on how to modulate DCs with tolerogenicity, but little attention has been directed towards the antigenic epitopes presented by DCs. In this study, we evaluated the roles of beta cell antigens presented by immature DCs (iDCs) in T1D prevention. At first, we established that beta cell antigen pulsing was required for iDCs to prevent T1D by using iDC pulsed with whole beta cell (NIT1) lysates. We further evaluated the capacity of different beta cell-derived antigenic peptides (Insulin B9-23, GAD78-97, GAD217-236, proInsulin C3-A19) in priming NOD splenic T cells in vitro. We discovered that GAD217-236 predominantly stimulated Th2 cells. Consistent with the in vitro results, 4 weekly intravenous injections of GAD217-236-pulsed iDCs significantly prevented diabetes in younger mice. Moreover, the same results were achieved when older NOD mice were treated. In the T cell recall experiments, it was noted that the splenocytes from the mice treated with GAD217-236-plused iDCs, in contrast to PBS-treated mice, produced significantly higher IL-4 and IL-10. Of interest, four beta cell antigenic peptides mentioned above stimulated the similar cytokine-producing pattern, suggesting that the immune response induced by GAD217-236-pulsed iDCs spreads to other beta cell antigens through epitope spreading.