Abstract

To investigate the possible role of cell mediated cytotoxicity in the pathogenesis or perpetuation of liver damage associated with alpha 1-antitrypsin (AAT) deficiency, peripheral blood lymphocytes (PBL) from 13 children with PiZZ phenotype who had had liver disease in infancy were incubated with autologous hepatocytes in a microcytotoxicity assay. There was a clear trend for cytotoxicity to increase with age and thus significantly increased cytotoxicity was found in four cases older than 2 years, while intermediate values were recorded in three children between 6 months and 2 years and normal values in children younger than 6 months. Fractionation of PBL into T and non-T-enriched subsets showed that both were involved in the cytotoxic reaction. A purified liver membrane lipoprotein preparation (LSP) inhibited both T and non-T-cell cytotoxicity suggesting that LSP is a major target antigen in this system. Control experiments performed in infants with neonatal hepatitis syndrome, but with normal Pi phenotype, showed consistently increased cytotoxicity values. Cell-mediated immune reactions directed against autologous hepatocytes develop late in the course of the liver disease associated with AAT deficiency. While this reaction cannot be involved in the pathogenesis of the initial liver lesion, it may contribute to perpetuation of liver damage.