Studies on experimental chronic active hepatitis in the rabbit. II. Immunological findings

The role played by humoral and cellular immune response to liver antigens in the pathogenesis of experimental chronic active hepatitis (CAH) was studied in rabbits which had been immunized with the two human liver-specific proteins LSP and LP2, with LSP alone, or with an extract of human skeletal muscle. Rabbits immunized with LSP, alone or with LP2, developed skin test reactivity and circulating antibody to homologous LSP; liver biopsy revealed immunoglobulin bound to the hepatocyte cell surface. It has been suggested that cellular immunity to homologous LSP or alternatively, antibody to an antigenic determinant shared by human and rabbit LSP, may play a role in the pathogenesis of experimental CAH, but both abnormalities were present in two rabbits which did not develop CAH despite observation for at least 18 months. Five normal rabbits given an intravenous injection of serum pooled from rabbits with CAH did not develop significant hepatic lesions. Immunity to homologous LSP or other hepatocyte cell surface antigens could not be detected in any rabbit which had been immunized with skeletal muscle, and hepatocytes from these rabbits did not have immunoglobulin on their cell surface. The pathogenesis of CAH in these animals is obscure. These findings suggest that mechanisms other than an auto-immune response to LSP play an important role in the pathogenesis of experimental chronic active hepatitis.