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

✍ Scribed by Hanns F. Löhr; Wolfgang Weber; Jörg Schlaak; Bernd Goergen; Karl-Hermann Meyer Zum Büschenfelde; Guido Gerken

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 920 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220110

✦ Synopsis

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 Be-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 t-3.9 vs. 13.0 2 3.2 vs. 8.0 ? 1.2; P < .01 and HBe: SI 16.6 5 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/ HBcAgand 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 Thl-like cytokine patterns. Follow-up of interferon (IFN) recipients showed simultaneous short-term increase of HBdHBe-