Administration of dendritic cells modified by RNA interference prolongs cardiac allograft survival.

Abstract

Systemic administration of immature donor-dendritic cells (DC) that are deficient in co-stimulatory molecules delays the onset of allograft rejection. However, it is not easy to control culture condition and guarantee that the administered DC are in the immature stages, which obviously affects their therapeutic effect. In this study, we attempted to inhibit expression of CD86 on DC using an RNA interference technology. The function of CD86(low) DC was determined by the influence on their capacity to stimulate T cell proliferation and by the effect of DC systemic administration on survival of cardiac allografts. CD86(low) DC stimulated low T cell proliferative responses in vitro and administration of CD86(low) DC prolonged survival of heart allografts in vivo. These results suggest that RNA interference is a useful approach to modify DC function, which has potentials for clinical application.