PROLIFERATIVE AND CYTOTOXIC T-CELL CLONES RECOGNIZE ENDOGENOUSLY SYNTHESIZED HBCAG IN AN ASYMPTOMATIC HBSAG CARRIER

The characterization of immun responses to hepatitis B virus is crucia l for the understanding of hepatitis B virus-caused liver disease. How ever, lack of a suitable sutologous effector-target cell system makes a precise study of the pathogenesis of hepatitis B difficult. In this study we established a model system by using autologous HBcAg-expressi ng Epstein-Barr virus-immortalized lymphoblastoid cell lines as stimul ator/target cells. T-cell cultures wer established by repetitive stimu laltion with recombinant HBcAg or autologous HBcAg-expressing lymphobl astoid cell lines. Both proliferative and cytotoxic T-cell clones were obtained from the peripheral blood of an asymptomatic HBsAg carrier. Clones T12 (CD8+) and T2B (CD4+) were cytotoxic clones specific agains t autologous lymphoblastoid cell lines expressing endogenously synthes ized HBcAg, whereas five CD4+ T-cell clones proliferated in response t o lymphoblastoid cell lines incubated with exogenous recombinant HBcAg and autologous HBcAg-expressing lymphoblastoid cell lines. These resu lts indicate that autologous HBcAg-expressing lymphoblastoid cell line s are appropriate stimulator/target cells for the study of HBcAg-speci fic T lymphocytes. By using this approach, we have demonstrated that b oth proliferative and cytotoxic T lymphocytes recognizing endogenously synthesized HBcAg are induced during chronic hepatitis B virus infect ion.