Effect of Immature Dendritic Cell Injection Before Heterotropic Cardiac Allograft

Although dendritic cells (DCs) are unrivaled for initiation of immune responses, the immunomodulatory capacity of chemically fixed DC has not been thoroughly evaluated. We monitored the tolerogenic capacity of chemically fixed DCs using allogeneic heart transplantations. Bone marrow progenitors were differentiated into immature DCs which were then chemically fixed and injected intravenously into recipient mice at 14 days before allogeneic heart transplantation. Chemically fixed DCs markedly prolonged graft survival in the major histocompatibility complex (MHC) I/II mismatch cardiac transplantation (B6 → B10.A; median survival time [MST] 12.5 days vs >70 days). T cells that encountered chemically fixed DCs showed attenuated apoptotic cell death and inactivated phenotypes after allogeneic heterotropic heart transplantation. Furthermore, when DCs from interleukin (IL)-10−/− mice were treated, the in vitro T-cell response was greater than that from IL-12−/− mice. We have suggested that the chemically fixed DCs may mediate peripheral T-cell tolerance, with therapeutic potential for allogeneic transplantation.