Experimental autoimmune hepatitis in mice after immunization with syngeneic liver proteins together with the polysaccharide of Klebsiella pneumoniae

Abstract

Experimental autoimmune hepatitis could be produced in SMA mice by monthly injections of syngeneic liver homogenate or liver-specific lipoprotein together with the polysaccharide of Klebsiella pneumoniae 03:K1 as a powerful adjuvant. Using a gel-diffusion technique, antibodies reacting with liver-specific lipoprotein and liver-specific membrane lipoprotein were detected in approximately 50% of sera from the immunized mice after an 8-mo period. After a full immunization schedule, 60%-80% of the livers of the sensitized mice developed infiltration of mono-nuclear cells consisting mainly of lymphocytes and plasma cells in portal areas, frequently associated with focal necrosis of hepatocytes. Moderate-to-severe piecemeal necrosis of hepatocytes appeared in 10 of 59 animals. However, a gradual decrease in the morphologic severity was observed 3-6 mo after cessation of injections. The transfer of splenic cells from animals with the damaged liver led to a hepatitis in recipients that was characterized by portal infiltration with mononuclear cells and by necrosis of liver parenchymal cells seen on day 14 after cell transfer. The suppressor cell activity determined by the ability of concanavalin A-activated cells to suppress blast transformation of splenic cells of normal SMA mice was significantly decreased (p less than 0.05) in mice immunized with a mixture of liver-specific lipoprotein and the polysaccaride of Klebsiella pneumoniae compared with mice immunized with the polysaccaride of Klebsiella pneumoniae alone or the polysaccaride of Klebsiella pneumoniae plus kidney lipoprotein.