Dendritic cells (DC) play a major role in natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activation leading to cell-mediated xenogeneic responses. In contrast, the use of in vitro differentiated regulatory DC may represent an attractive approach to protect porcine endothelial cells (pEC) from human cell-mediated immune responses. In this study, we evaluated the potential of human regulatory DC to reduce xenogeneic NK cell and CTL responses to pEC.