Different mechanisms responsible for in vitro cell-mediated cytotoxicity to autologous hepatocytes in children with autoimmune and HBsAg-positive chronic liver disease.
To investigate mechanisms of hepatocyte injury, lymphocytes from 41 children with chronic liver disease were incubated with autologous liver cells in a microcytotoxicity assay. Cytotoxicity was significantly increased in 18 of 25 patients with chronic hepatitis B virus (HBV) infection, in five of nine with "autoimmune" chronic active hepatitis (CAH), and in only one of seven with histologically inactive liver disorders. There was a good correlation between cytotoxicity and biochemical and histologic markers of disease activity in children with autoimmune CAH, whereas in HBsAg-positive disease a positive correlation was found only with serum alanine aminotransferase (SGPT). Children with autoimmune CAH receiving steroid treatment had normal cytotoxicity, whereas increased values were found in two of three HBsAg-positive patients receiving prednisolone. Fractionation studies revealed that non-T cells were cytotoxic in both autoimmune and HBcAg-positive chronic liver disease. T cell cytotoxicity was exclusively found in children with chronic HBV infection, particularly with HBc antigenemia. Blocking experiments showed that T-lymphocytes from HBsAg-positive children reacted with HBV core antigen on the hepatocyte surface. Non-T cells were directed against hepatocyte membrane antigens in both HBsAg-positive and HbsAg-negative children. These results suggest that different immune mechanisms of liver damage are involved in autoimmune and HBsAg-positive chronic liver disease.
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001667:Binding, Competitive; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D006510:Hepatitis B Antibodies / Q000502:physiology; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007223:Infant; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008214:Lymphocytes / Q000145:classification / Q000276:immunology; D008297:Male
D000911:Antibodies, Monoclonal; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase