The Luo Lab studies tolerance mechanisms for transplantation in rodents as well as non-human primate models. These models include allogeneic islet, heart and kidney, and xenogeneic islet transplantation. Transplant tolerance is induced by infusion of donor cells treated with the chemical cross-linker ethylcarbodiimide (ECDI). Using a stringent full MHC-mismatched strain combination, we have shown in an allogeneic islet cell transplant model that two infusions of ECDI-treated donor cells prior to and after transplantation led to indefinite graft survival in over 90% of the transplant recipients in the absence of any immunosuppression. This tolerance strategy takes advantage of the tolerogenic recognition of apoptotic donor cells by recipient CD11c dendritic cells, and is associated with up-regulation of regulatory T cells and down-regulation of anti-donor T and B cell responses. The same strategy has been applied to allogeneic heart and kidney transplant, as well as xenogeneic islet transplant (rat-to-mouse, pig-to-mouse) with robust tolerance efficacy. We are currently applying the same strategy to monkey-to-monkey (allogeneic) and pig-to-monkey (xenogeneic) islet transplantation. Our ultimate goal is to test this tolerance strategy in human-to-human (allogeneic) and pig-to-human (xenogeneic) solid organ and/or tissue transplantation. Additional ongoing efforts in the lab also focus on: (1) understanding how viral infections at various stages (acute, chronic, latent) can influence tolerance efficacy and stability; (2) designing nanoparticle-based cell-free tolerance strategies for allogeneic and xenogeneic transplantation.