Xenotransplantation represents an attractive alternative to overcome the human organ shortage in clinical transplantation. Nevertheless, delayed cell-mediated xenograft rejection by natural killer (NK) cells and cytotoxic T lymphocytes (CTL) remains an obstacle for successful xenotransplantation. By contrast, tolerogenic DC represents a promising tool for the promotion of transplantation tolerance. The main goal of the present thesis was to evaluate whether tolerogenic DC could be used as cell-based therapy to protect xenografts. We demonstrated that human monocyte-derived DC, generated in the presence of rapamycin (Rapa-DC) or IL-10 (IL-10-DC), could modulate human anti-pig NK cell and CTL responses in vitro. Finally, we investigated the potential of autologous bone marrow-derived DC, differentiated in the presence of IL-10, to prevent xenograft rejection in a rat-to-mouse islets xenotransplantation model. When co-transplanted with rat islets under the kidney capsule, IL-10-DC significantly prolonged islets xenograft survival. Recipients of IL-10-DC demonstrated higher infiltration of CD4+ FoxP3+ T-cells in islets xenograft.