ENHANCEMENT OF BABOON LIVER ALLOGRAFTS WITH NONCYTOTOXIC PREPARATIONS OF ALLOIMMUNE IgG

Abstract

SUMMARY In previous studies we have reported significant prolongation of baboon liver allograft survival by passive enhancement with a hyperimmune, polyspecific lymphocytotoxic alloantiserum (PSS) or combined passive and active enhancement with PSS and donor bone marrow (BM) cells. A very florid form of rejection in certain of these animals raised the possibility of damage to the graft by the passively administered C-fixing antibody. A papain digest of the polyspecific IgG (PD-IgG) and the electrophoretically fast migrating fraction of PS-IgG (prepared by DEAE-cellulose chromatography) reduced but did not abolish lymphocytotoxicity, and did not eliminate the occurrence of this type of rejection. In this study we report the enhancing properties of two non-cytotoxic preparations of PS-IgG. A papain digest of the electrophoretic fast fraction (PDF-IgG), when given as a single injection of 10 mg/kg at the time of liver transplantation, prolonged graft survival significantly (mean survival time (MST) 41 ± 9 days) and was superior to cytotoxic PSS (MST 32 ± 4 days). Succinylated PS-IgG (Suc-IgG) also prolonged allograft survival significantly (MST 29 ± 4 days) but was somewhat inferior to PSS. Features suggestive of hyperacute rejection were not observed in these groups. It is felt, however, that the mechanism of potential injury of a graft by alloantibody is not confined to its C-fixing ability because large doses of cytotoxic, electrophoretically slow IgG (S-IgG) significantly prolonged liver allograft survival without production of histological features of hyperacute rejection. The ability of these subfractions to trigger antibody-dependent lymphocytotoxicity may be relevant. Preliminary studies indicate that PDF-IgG is least active in this regard.