Prevention of acute rejection by RelB siRNA-silenced dendritic cells

Abstract

Objective To prevente acute rejection in cardiac transplantation by using tolerogenic dendritic cells (DC).Methods The mixed lymphocyte reaction (MLR) was performed by RelB siRNA-DC with allogenic antigen-specific T cells.The apoptosis rate of T cells and the ratio of CD4 + CD25 + Foxp3 + regulatory T cells were detected by using flow cytometry after MLR.In the murine model of cardiac transplantation,the survival time was observed after infusion of RelB siRNA-DC before transplantation.HE staining was used to examine the rejection degree in the specimens of allografts.Results Mature DC and LucR siRNA DC could stimulate the proliferation of T cells more strongly than immature DC and RelB siRNA-DC (P ＜ 0.05).The RelB siRNA-DC could induce allogeneic T cell hyporesponsiveness,but had no specific reactivity on the third kind T cells (P ＞ 0.05).RelB siRNA-DC induced T cell apoptosis [(29.21 ± 7.55)％,P ＜ 0.05] and promoted T cells differentation into CD4 + CD25 + Foxp3 + regulatory T cells [(65.3 ± 12.6)％,P ＜ 0.05].In the mouse cardiac transplantation model,infusion of donor-derived Lenti-RelB siRNA-DC could prolong the graft survival time (P ＜ 0.05) and reduce rejection occurrence.Conclusion Donor-derived RelB-siRNA-induced tolerogenic DC can significantly induce immune tolerance in vitro and in vivo. Key words: Dendritic cell; Heart transplantation; Rejection; Regulatory T cell