The chimeric nature of the transplanted liver was first shown in our long-surviving human recipients of orthotopic hepatic allografts in 1969. 1 When liver grafts were obtained from cadaveric donors of the opposite sex, karyotyping studies showed that hepatocytes and endothelium of major blood vessels retained their donor specificity, whereas the entire macrophage system, including Kuppfer cells, was replaced with recipient cells. 2 Where donor cells that had left the liver had gone was unknown, but their continued presence was confirmed by the acquisition and maintenance in recipient blood of new donor-specific immunoglobulin (Gm) types1, 3 and red-blood-cell alloantibodies, if donors with ABO non-identity were used. 4 Davies et al5 attributed the secretion of new soluble HLA class I antigens of donor type to transplanted hepatocytes. However, these HLA molecules come from bone-marrow-derived macrophages and/or dendritic cells, 6 and probably have the same origin from migrated donor cells as the additional Gm types and red-cell antibodies.

Although this early evidence of systemic mixed allogeneic chimerism was circumstantial, we have recently shown with both anatomical and molecular techniques the presence, in clinically stable patients, of peripherally located donor cells many years after liver replacement. For instance, in patients with type IV glycogen storage disease, a disorder in which an insoluble amylopectin-like polysaccharide accumulates throughout the body because of a deficiency in a branching enzyme, we found resorption of extrahepatic amylopectin after liver replacement. 7 This process could not be explained until the migrated donor cells, which had acted as enzyme couriers, were identified by both HLA monoclonal antibodies (fig 1) and polymerase chain reaction (PCR) studies (fig 2) in the biopsied myocardium and skin of 2 patients, 33 and 91 months after hepatic transplantation.