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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
Author(s) -
Sprinzl M. F.,
Russo C.,
Kittner J.,
Allgayer S.,
Grambihler A.,
Bartsch B.,
Weinmann A.,
Galle P. R.,
Schuchmann M.,
Protzer U.,
Bauer T.
Publication year - 2014
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12189
Subject(s) - medicine , hepatitis b virus , seroconversion , immunology , peripheral blood mononuclear cell , t cell , hepatitis b , population , virology , virus , biology , immune system , in vitro , biochemistry , environmental health
Summary 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 CD 4 and CD 8 T cells were analysed ex vivo by flow cytometry. HBV S‐ and core‐specific CD 4 T‐cell numbers modestly increased within 8 weeks of IFN administration ( P = 0.0391 and P = 0.0195), whereas HBV ‐specific CD 8 T cells in general showed only minor changes under IFN add‐on therapy. Functionality of HBV ‐specific CD 4 but not CD 8 T cells positively correlated with serum transaminase activity. In addition, we observed an increase in CD 4 T cells producing tumour necrosis factor‐α ( TNF α) without antigen restimulation ( P = 0.0039), which correlated with elevated transaminases. During IFN add‐on therapy, two patients developed an anti‐ HB s 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 TNF α‐monofunctional CD 4 T‐cell population. Although the observed T‐cell responses did not correlate with HB s A g seroconversion, we expect additional insights into the immunopathogenesis of hepatitis B , following the characterization of the newly identified TNF α‐monofunctional T‐cell population.