Cell-mediated immunity to liver antigen in toxic liver injury. I. Occurrence and specificity

To investigate the possible role of cell-mediated immunity in the pathogenesis of liver disease lymphocyte function was studied in CBA mice in which predictable sublethal liver necrosis had been included by the administration of the hepatotoxin carbon tetrachloride (CCl4). Non-specific lymphocyte function, as assessed by the response to the mitogen phytohaemagglutinin (PHA) was normal in over 90 percent of the animals. Forty-three per cent of the treated mice demonstrated specific lymphocyte sensitivity to liver antigen preparations. Such specific sensitivity was transient and apparent in only one case for more than 2 weeks after the CCl4 treatment. The lymphocyte sensitization was not reproduced by the addition of CCl4 to the lymphocyte cultures. There was no correlation between the severity of the liver disease and the detection of sensitized lymphocytes. Although these data may not be extrapolated directly to human liver disease, they demonstrate that cell-mediated immune reactivity to liver-derived antigens can occur as a result of non-immunological toxic liver injury.