Prevention of sensitization and hyperacute rejection in liver and heart xenografts by FK 506 plus donor antigens.

WE have. observed that FK S06 (FK) preve~ted the inductIon of hyperacute reJectIOn (HAR) In hamster-to-ratliver (OLTX) and heart (HTX) transplant models and analyzed the mechamsms. 1.5 x 107 hamster hepatocytes (HC) or a minced heart as source of xenoantigens were given to prospective recipients on day -6. with or without FK (I mg/kg/d x fl). OL TX and HTX were performed on day O. Xenoantigen alone induced HAR that correlated with high titer of complement-dependent cytotoxic antibody (CDC). Additionally. immunosuppression with FK resulted in prevention of HAR and improved survival of OLTX recipients in the first 3 postoperative weeks (l' < .05). with evidence of reduced antibody in the grafts. Even though FK did not eliminate total IgM amount and natural antibody titers. target-specific IgM. which is responsible for HAR. was reduced in the antigen ~ FK-treated group as compared with that with antigen alone. Furthermore. the sera from long-term survivors of OL TX did not inhibit CDC