Characterization of Forssman and Other Antigen/Antibody Systems in Vascularized Mouse Heart to Rat Xenotransplantation

In the present study, the nature of hyperacute xenograft rejection was closely studied in a vascularized mouse‐to‐rat transplantation model. Antibodies against mouse heart, erythrocytes and lymphocytes and against the Forssman antigen were raised in the rat. Upon heterotopic heart transplantation the respective antisera were intravenously (i.v.) injected. Passive transfer of antiheart, antierythrocyte or antilymphocyte serum resulted in hyperacute rejection of the transplanted mouse heart. Subfractionation of the antiheart serum showed that the capacity to induce hyperacute rejection was carried by the immunoglobulin (Ig)G fraction. When antierythrocyte serum adsorbed with mouse erythrocytes was administered the cardiac grafts remained beating. To the contrary, antilymphocyte serum adsorbed with erythrocytes still had the capacity to induce hyperacute rejection. None of the rats that had previously been challenged with the Forssman antigen rejected their grafts hyperacutely. Subsequent investigations by electron microscopy revealed that the Forssman antigen is expressed on dendritic cells (DC) adjacent to the vessels, but not on the vascular endothelium, thus explaining the inability of the anti‐Forssman serum to induce hyperacute rejection. Taken together, we have demonstrated the existence of several xenoantigens that can be targets for antibody‐mediated rejection, suggesting that more than one relevant xenoantigen exists also in more distantly related combinations, such as the pig‐to‐human combination.