Proliferative response of CD4+ T cells and hepatitis B virus clearance in chronic hepatitis with or without hepatitis B e-minus hepatitis B virus mutants.
To assess the significance of cell-mediated immunity, T cells were derived from the peripheral blood and liver tissue of hepatitis B virus (HBV)-infected patients and controls. The analysis of the 3H-thymidine-uptake in response to a panel of recombinant HBV antigens revealed that peripheral blood mononuclear cells (PBMC) of the 25 viremic patients with inflammatory active, chronic hepatitis B, 16 with wild-type and nine with HBe-minus HBV mutant infection, showed stronger proliferative responses to HBc and HBe antigens than 16 asymptomatic nonviremic HBsAg carriers with normal aminotransferase levels (HBc: SI 19.3 +/- 3.9 vs. 13.0 +/- 3.2 vs. 8.0 +/- 1.2; P < .01 and HBe: SI 16.6 +/- 4.0 vs. 10.7 +/- 3.5 vs. 6.9 +/- 1.5; P < .05). In 15 patients with acute self-limited hepatitis B, however, significantly stronger HBc antigen-specific T-cell responses were observed during HBV clearance and HBe/anti-HBe seroconversion, whereas in nine completely HBV-immunized patients only minor proliferative responses to HBV antigens were observed. Six HBe/HBcAg- and two HBeAg-specific CD4+ T-cell lines could be expanded from liver tissue and peripheral blood of six viremic patients with chronic hepatitis B. Irrespectively of HBV mutations the HBV-specific activation of the T-cell lines was restricted by the presence of HLA-DR molecules and resulted in the release of Th1-like cytokine patterns. Follow-up of interferon (IFN) recipients showed simultaneous short-term increase of HBc/HBe-specific T-cell reactivities in responder patients during HBV clearance and HBe/anti-HBe seroconversion, whereas in nonresponders high virus load and HBV-specific immune responses were in imbalance.(ABSTRACT TRUNCATED AT 250 WORDS)
Löhr
H F
HF
I. Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, Germany.
Weber
W
W
Schlaak
J
J
Goergen
B
B
Meyer zum Buschenfelde
K H
KH
Gerken
G
G
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002455:Cell Division; D002908:Chronic Disease; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009154:Mutation
D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha