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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Kakumu
S
S
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Ishikawa
T
T
Wakita
T
T
Yoshioka
K
K
Takayanagi
M
M
Tahara
H
H
Kusakabe
A
A
D000208:Acute Disease; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D007371:Interferon-gamma