Donor-Specific Allograft Tolerance by Administration of Recipient-Derived Immature Dendritic Cells and Suboptimal Immunosuppression

Abstract

We recently showed that injection of recipient-type immature bone marrow-derived dendritic cells (iBMDCs) the day before transplantation induced a significant prolongation of allograft survival. This study aimed at improving the administration protocol to induce allograft tolerance. Various amounts of iBMDCs were administered to syngeneic LEW.1A rats before and after transplantation of an allogeneic LEW.1W heart, with or without additional suboptimal immunosuppression. Allograft survival was not improved by repeated injections of syngeneic iBMDCs or by additional treatment with low-dose rapamycin. Combining injections of iBMDCs and LF 15-0195 showed a striking synergistic effect and induced definitive allograft acceptance in 92% of recipients. Tolerant recipients accepted donor-type, but not third-party type skin grafts, suggesting the development of regulatory mechanisms capable of maintaining donor-specific tolerance. The reported findings may contribute to the development of new therapeutic strategies to induce transplantation tolerance in humans.