ROLE OF ANTIBODY-SYNTHESIS AND COMPLEMENT ACTIVATION IN CONCORDANT XENOGRAFT RETRANSPLANTATION

A mouse-to-rat heart retransplantation model was used to study the eff ects of complement depletion and antibody production with regard to gr aft survival and anti-donor antibody specificity. Retransplantation wa s performed 3 weeks after the first transplantation in the presence or absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated anim als rejected their first graft after 3 days and retransplantation resu lted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endoth elium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graf t vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted wi th hamster antigens and a hyperacute rejection of a hamster heart graf t occurred in a mouse-sensitized rat. Immunofluorescent staining revea led that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolong ed the survival of the first graft by a median of 8 days. Continuous t reatment until retransplantation resulted in a prolongation to 30 (20- 127) min of the survival of the second graft and no increase in antibo dy titers against mouse antigens was observed. However, immunofluoresc ent staining revealed a weak binding of anti-mouse antibodies of the I gM subclass in the rejected mouse heart graft. Additional complement d epletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but h istology revealed massive mononuclear infiltration. In conclusion, xen ograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatme nt is administered from the day of transplantation, this reduces the s ynthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.