In-vitro cell-mediated cytotoxicity for autologous liver cells in chronic non-A, non-B hepatitis.

To investigate the possible mechanisms of liver cell injury in chronic non-A, non-B (NANB) hepatitis, peripheral blood lymphocytes (PBL) from 16 patients with chronic NANB hepatitis were incubated with autologous hepatocytes in a microcytotoxicity assay. Significant cytotoxicity was demonstrated in 11 patients. T-enriched lymphocytes exhibited significantly greater cytotoxicity than non-T enriched cells. No significant inhibition of cytotoxicity was observed following preincubation of the liver cells with either monoclonal or polyclonal anti-HBc, or monoclonal anti-HBs, or addition of either purified HBsAg or recombinant HBcAg to the culture, indicating that there was no detectable cross-reactivity in this system between hepatitis B virus (HBV) and NANB-associated antigen(s). Preincubation of the patients' hepatocytes with polyclonal IgG purified from a serum of a patient who recovered from an acute NANB hepatitis, did not significantly alter cytotoxicity. Liver cell surface-bound IgG was detected by immunofluorescence in only two of the patients, a finding consistent with existing evidence of poor antibody responses to both liver membrane and NANB-associated antigens. Control experiments using PBL from allogeneic normal donors exhibited normal cytotoxicity for the patients' hepatocytes supporting the hypothesis that antibody-dependent cell-mediated cytotoxicity (ADCC) is unlikely to play a significant role in this clinical setting.