Interferon-gamma production specific for hepatitis B virus antigen by intrahepatic T lymphocytes in patients with acute and chronic hepatitis B.

Abstract

Studies were undertaken to determine whether intrahepatic lymphocytes have a greater cellular immune response specific for hepatitis B virus (HBV) antigen than peripheral blood lymphocytes in HBV-infected man. HB nucleocapsid antigen-stimulated interferon-gamma (IFN-gamma) production of lymphocytes was measured in acute self-limited hepatitis (AH) (eight cases) and chronic hepatitis (CH) (14 cases). In both patient groups, basal IFN-gamma levels without any stimulation were higher in the hepatic T cells than in the peripheral T cells. The values in cultures from blood and liver were larger in AH than in CH. Alternatively, IFN-gamma response to HBcAg and HBeAg was less in hepatic T cells than in the corresponding blood cultures; T cell response was HLA class II restricted. Cell flow cytometry study showed that in all patient groups, percentages of CD3+, CD8+, and HLA-DR+ cells were significantly greater in liver than in peripheral blood, whereas the proportion of hepatic CD4+ cells was decreased, compared with that in peripheral CD4+ cells. These findings suggest that liver infiltrates are already activated in vivo to produce IFN-gamma, particularly in patients with AH. The changes in the proportion of lymphocyte subsets may be responsible for the altered IFN-gamma response of hepatic T cells.