The cytotoxic effect of peripheral lymphocytes on chicken red blood cells (ChRBC) coated with purified hepatitis B surface antigen (HBsAg) has been studied as an in vitro parameter of cell-mediated immunity in acute and chronic infection with hepatitis B virus. Using this technique, the mean cytotoxic index of lymphocytes from patients with acute hepatitis B (29·13 ± 20·88) was significantly higher than that obtained with lymphocytes from control subjects (6·53 ± 3·75). Only 33·3% of the patients with HBsAg-positive chronic active hepatitis exhibited lymphocyte cytotoxicity to HBsAg-coated target cells and the mean cytotoxic index (11·66 ± 6·60) was in these cases significantly lower than that found in acute hepatitis B. Healthy chronic carriers of HBsAg failed to show lymphocyte cytotoxicity to target cells. The effector cells detected in acute hepatitis B by this in vitro assay have been demonstrated to be T-lymphocytes, as T-cell depleted subpopulations lacked cytotoxic activity. Target cell lysis could be blocked by addition of HBsAg-coated unlabelled ChRBC as well as of purified HBsAg in the culture tubes. It is suggested that damage to the liver cells in acute hepatitis B is related to the presence of cytotoxic T-lymphocytes reacting with HBsAg on the surface of infected hepatocytes. An inadequate lymphocyte response to the antigen may be responsible for the persistence of the infection in the liver with varied clinical manifestations and associated hepatic lesions.
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