Effect of CD40 silenced dendritic cells by RNA interference on mice skin allograft rejection

Abstract

Aim: Tolerogenic dendritic cells (DCs) play a critical role in inducing and maintaining tolerance. CD40 is a member of tumor necrosis factor receptor super family and is a potent T-cell costimulatory molecule. Therefore, in this study we evaluated the effect of CD40 silenced DCs by RNA interference on mice skin allograft rejection. Materials & methods: Skin transplantation was performed from C57BL/6 to BALB/c mouse. Skin allograft recipients were assigned to four groups (n = 5). CD40 downregulated DCs were injected to the BALB/c mice intravenously 7 days before transplantation. Then, graft survival time, Treg generation, CD4+ and CD8+ T cells infiltration and cytokine levels in serum of this group were compared with those of untreated and cyclosporine groups. Results: In comparison with untreated group, BALB/c mice injected with CD40 siRNA transfected DCs showed an increased graft survival time, Treg cells, IL-4 and IL-10 cytokine levels as well as decreased number of intragraft CD4+ and CD8+ T cells. IFN-γ and IL-12 secretion were diminished, too. Conclusion: Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.