T lymphocyte-mediated cytotoxicity in HBsAg-positive liver disease.

It has been suggested that cellular immune responses to the hepatitis B virus are of importance in the production of liver cell damage in both acute and chronic hepatitis. An assay has now been developed which detects lymphocytes cytotoxic for target cells coated with the hepatitis B surface antigen (HBsAg). The reaction could be blocked by prolonged pre-incubation of lymphocytes with highly purified HBsAg and studies with lymphocyte subpopulations have shown that T lymphocytes were the principle effector cells. When lymphocytes from twenty-three patients with acute hepatitis were used, cytotoxic T cells were demonstrable during the recovery phase, but not in the first 3 weeks of the illness. However, when these same lymphocytes were extensively washed, cytotoxicity was then detected in all the patients, even at the time of presentation. In patients with HBsAg-positive chronic liver disease the results with the standard assay were largely within the normal range, but again with extensive lymphocyte washing cytotoxicity was detected in all of the patients with untreated chronic active hepatitis and in five out of six with more minor histological lesions. The results in five carriers with normal liver histology were completely different, cytotoxicity remaining undetectable even after the extensive washing procedure. The results suggest that blocking factors, possibly antigen or antigen–antibody complexes, could be interfering with the detection of sensitized T cells in patients with acute and chronic hepatitis, but that there is a true absence of sensitization to HBsAg in healthy carriers with normal liver histology.