T lymphocyte sensitization to hbcag and T cell‐mediated unresponsiveness to HBsAg in hepatitis B virus‐related chronic liver disease

Using a newly developed indirect T lymphocyte migration inhibition test, cell‐mediated immunity to HBsAg and HBcAg was directly and simultaneously examined in a total of 21 patients with HBsAg‐positive chronic liver disease (CLD), and in seven subjects whose sera contained anti‐HBs (2 previous acute hepatitis B; 4 hepatitis B vaccine recipients and 1 chronic active hepatitis). T cell sensitization to HBcAg was invariably detected in the HBsAg‐positive CLD patients tested (12/12), whereas T cell sensitization to HBsAg was not present in any of the patients (0/21). In contrast, T cell sensitization to HBsAg was present in all anti‐HBs‐positive subjects. These results support the hypothesis that the cellular immune response to HBcAg, rather than to HBsAg, is implicated in the pathogenesis of HBsAg‐positive CLD. Moreover, the observation that the addition of T cells from patients with HBsAg‐positive CLD to T cells from anti‐HBs positive subjects in a ratio of 1 to 9 reversed their sensitization to HBsAg, suggests that a hyperactivity of HBsAg‐specific suppressor T cell population may be responsible for persistent HBs antigenemia.