LYMPHOCYTE CYTOTOXICITY AGAINST HBsAg-COATED HEPATOCYTES IN PATIENTS WITH CHRONIC HEPATITIS

I. Significance of T-cell Mediated Cytotoxicity

Abstract

T cells from about 30% of patients with chronic hepatitis showed significantly higher cytotoxicity against HBsAg-coated hepatocytes than healthy subjects, whereas non of the patients showed significant cytotoxicity against albumin-coated hepatocytes. Among patients with HBsAg-negative chronic hepatitis significant T-cell cytotoxicity against HBsAg-coated hepatocytes was observed in patients having cellular antibody to HBsAg detected by lymphocyte blast transformation responses. Similar positive T-cell mediated cytotoxicity was observed both in patients with convalescent acute B hepatitis and healed acute B hepatitis, suggesting that positive T-cell cytotoxicity in HBsAg-negative patients represents anamnestic responses to HBsAg of sensitized T lymphocytes and has no significant pathogenetic roles in hepatocyte destruction because HBsAg is seemed to be absent in their hepatocytes.
Significant T-cell cytotoxicity against HBsAg-coated hepatocytes was also found in patients with HBsAg-positive chronic hepatitis, having cellular antibody to HBsAg and low HBsAg titers in their sera. Levels of serum transaminase were significantly higher in patients showing positive T-cell cytotoxicity than those showing negative one.
In our experimental systems, HLA systems seemed not to be responsible for occurrence of the Tcell cytotoxicity reactions as seen in cytotoxic T-cell mediated cytotoxicity against virus-infected target cells. In consideration of the parallel occurrence of the positive T-cell cytotoxicity and cellular anti-HBs antibody, and the results of positive lymphotoxin assay in cytotoxicity-positive patients, it is suggested that T-cell mediated cytotoxicity in our systems seemed to be mediated by lymphokine producing T-cells as a result of delayed hypersensitivity reaction.
Non T-cells from both patients with chronic hepatitis and healthy subjects showed significantly higher cytotoxic activity to HBsAg-coated heaptocytes, when compared to those to albumin-coated hepatocytes. The cytotoxic values of non T-cells from patients with chronic hepatitis were higher than that of healthy subjects. This cytotoxic reactivity was interpreted as a spontaneous cellmediated cytotoxicity against HBsAg-coated hepatocytes.