title: Hepatitis B virus-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment.
abstract: The effect of pegylated interferon-α (IFN) add-on therapy on HBV-specific T-cell responses was evaluated in 12 patients with stable, undetectable hepatitis B virus (HBV) load under nucleos(t)ide analogue therapy. Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, 24 and 48 of IFN add-on therapy. Quantity and quality of circulating HBV S- and core-specific CD4 and CD8 T cells were analysed ex vivo by flow cytometry. HBV S- and core-specific CD4 T-cell numbers modestly increased within 8 weeks of IFN administration (P = 0.0391 and P = 0.0195), whereas HBV-specific CD8 T cells in general showed only minor changes under IFN add-on therapy. Functionality of HBV-specific CD4 but not CD8 T cells positively correlated with serum transaminase activity. In addition, we observed an increase in CD4 T cells producing tumour necrosis factor-α (TNFα) without antigen restimulation (P = 0.0039), which correlated with elevated transaminases. During IFN add-on therapy, two patients developed an anti-HBs seroconversion, only one of whom showed a relevant increase in HBV-specific T cells. In conclusion, IFN add-on therapy of chronic hepatitis B increased HBV-specific T-cell responses and affected a previously unrecognized TNFα-monofunctional CD4 T-cell population. Although the observed T-cell responses did not correlate with HBsAg seroconversion, we expect additional insights into the immunopathogenesis of hepatitis B, following the characterization of the newly identified TNF α-monofunctional T-cell population.
authors.affiliation: Institute of Virology, Technische Universität München / Helmholtz Zentrum München, Munich, Germany; Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
authors.forename: M F
authors.initials: MF
authors.lastname: Sprinzl
authors.forename: C
authors.initials: C
authors.lastname: Russo
authors.forename: J
authors.initials: J
authors.lastname: Kittner
authors.forename: S
authors.initials: S
authors.lastname: Allgayer
authors.forename: A
authors.initials: A
authors.lastname: Grambihler
authors.forename: B
authors.initials: B
authors.lastname: Bartsch
authors.forename: A
authors.initials: A
authors.lastname: Weinmann
authors.forename: P R
authors.initials: PR
authors.lastname: Galle
authors.forename: M
authors.initials: M
authors.lastname: Schuchmann
authors.forename: U
authors.initials: U
authors.lastname: Protzer
authors.forename: T
authors.initials: T
authors.lastname: Bauer
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000637:Transaminases / Q000097:blood
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D000637:Transaminases
keywords: hepatitis B surface antigen; immune response; interferon; seroconversion; tumour necrosis factor