부산대학교 도서관

There is a constant shortage of human organs suitable for transplantation which has led the focus of research to the possibility of transplanting porcine organs into human. In order to overcome the immunological barriers in xenotransplantion major progresses have been made in the last decades regarding antibody-mediated and complement mediated hyperacute rejection, yet coagulation incompatibilities as well as innate and adaptive xenogeneic immune responses still remain problematic. Regarding the latter, regulatory T cells have been of special interest because of their immunosuppressive capacities. Polyspecific regulatory T cells have been shown to be able to prevent xenogeneic graft versus host disease but only under lymphopenic conditions, which is not the case after transplantion. Donor-specific regulatory T cells may therefore offer another more promising approach in cellular therapy in immunocompetent specimens. Recently, we developed a protocol for the ex vivo generation of alloantigen-specific human regulatory T cells by activation with donor-derived activated B cell blasts. These alloantigen-specific regulatory T cells were far more potent in controlling T cell mediated immune responses. Transferring this protocol into a xenogeneic setting, we succeeded in expanding porcine B cells by activation with the human CD40-ligand. Activation of polyspecific human regulatory T cells led to the generation of xenospecific regulatory T cells, which show promising immunosuppressive properties when compared to polyspecific regulatory T cells in preliminary experiments. [ABSTRACT FROM AUTHOR]