Transplantation of Chimeric Organs: Implications for the Passenger-Cell Concept
The major contribution of marrow-derived Ia-positive dendritic cells (DCs) in initiating alloimmune reaction both in vivo (Elkins and Guttmann 1968) and in vitro (Steinman and Witmer 1978) forms the basis of the passenger concept of allograft rejection. Elimination of dendritic cells is thought to be a useful approach in reducing graft immunogenicity (Lafferty 1980). Pretreatment of grafts with cytotoxic antibodies directed against, Ia-positive cells of islets in vitro has yielded promising results (Faustman et al. 1981) but is not feasible in vascularized organ transplantation. Many attempts to deplete these cells using donor pretreatment by cytotoxic agents (Guttman et al. 1969) failed possibly because the grafts were harvested prior to complete depletion of DCs (Hart and Fabre 1981 a). The interval between the cytoreductive pretreatment and graft harvesting is limited by hemopoietic failure and may be overcome by allogenic bone marrow reconstitution (Tutschka and Santos 1975) enabling grafts to be removed later on. Furthermore, chimeric animals provide a model to investigate the role of dendritic cells in graft rejection (Esses and Halloran 1983; Woodward et al. 1982) .The relative contribution of donor DCs to the rat heart and pancreas allografts was studied by transplantation of chimeric organs. Allograft chimeras were created to have the majority of DCs syngenic with prospective allograft recipients. Gradual disappearance of recipient type and repopulation with donor-type Ia-positive cells taking several weeks could be demonstrated.
KeywordsAllograft Survival Skin Allograft Pancreas Graft Pancreas Allograft Bone Marrow Reconstitution
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