Hepatitis B core antigen-specific IFN-gamma production of peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection.
To evaluate the specificity of cellular immune response to hepatitis B virus (HBV) Ag in patients with chronic HBV infection, we have measured IFN-gamma production and proliferation of PBMC of 16 patients with chronic active hepatitis (CAH), 17 asymptomatic carriers of HBV (ASC), 6 anti-hepatitis B surface (HBs)-positive subjects, and 6 control individuals with ELISA procedure and [3H]thymidine incorporation. There was no significant increase in the mean proliferative response to recombinant HB surface and core Ag (rHBsAg and rHBcAg), nor was IFN-gamma production elicited with rHBsAg in any group. In contrast, PBMC of HBeAg-positive and anti-HBe-positive CAH patients, and anti-hepatitis B "e" Ag (HBe)-positive ASC showed significantly enhanced IFN-gamma production in response to HBcAg, whereas those of HBeAg-positive ASC and anti-HBs-positive subjects did not respond to HBcAg. The maximal response was observed in a 5-day culture with 500 ng/ml of rHBcAg when assessed by stimulation index value. Monocytes did not demonstrate an increased suppressor or helper activity for IFN-gamma production in these patients. T cell subset fractionation revealed that CD4+ cells were main population of IFN-gamma production specific for HBcAg and CD8+ cells did not suppress IFN-gamma production of CD4+ cells. Furthermore, CD4+ cells of HBeAg-positive ASC generated lesser amounts of IFN-gamma than HBeAg-positive CAH patients did. These results show that the measurement of IFN-gamma production is useful to determine cellular immune response to HBV Ag and suggest that IFN-gamma production depends on the helper activity of CD4+ T cells sensitized to HBcAg.
Inoue
M
M
Third Department of Medicine, Nagoya University School of Medicine, Japan.
Kakumu
S
S
Yoshioka
K
K
Tsutsumi
Y
Y
Wakita
T
T
Arao
M
M
D000939:Epitopes / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000276:immunology
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D014614:Vaccines, Synthetic; D007371:Interferon-gamma