CD16 <sup>+</sup> γδ T cells mediate antibody-dependent cellular cytotoxicity and associate with viral control in chronic hepatitis B virus infection
BACKGROUND: Chronic hepatitis B virus (HBV) infection is characterised by immune dysfunction. While conventional T cell responses have been extensively studied, the role of γδ T cells, innate-like cytotoxic lymphocytes enriched in the liver, remains incompletely understood. OBJECTIVE: To characterise γδ T cell subsets in HBV infection and assess their association with viral control and antibody-dependent cellular cytotoxicity (ADCC). DESIGN: Peripheral blood from patients with chronic (n=83) and acute (n=16) HBV infection, healthy controls (n=31), and cord-blood donors (n=3) was analysed using multiparameter flow cytometry, single-cell RNA sequencing and in vitro ADCC assays. RESULTS: γδ T cells were expanded and highly functional in acute HBV but reduced and partially impaired in chronic infection. Neonatal cord-blood-derived γδ T cells lacked CD16 expression and displayed limited ADCC potential. CONCLUSIONS: γδ T cells mediate antibody-dependent antiviral immunity in HBV infection. Their inverse association with HBcrAg links γδ T cell-mediated ADCC to viral control and highlights this pathway as a target for HBV cure strategies.
Authors
- Melanie Urbanek‐Quaing (ORCID: https://orcid.org/0000-0002-3629-9011)
- Roni Souleiman
- Markus Cornberg (ORCID: https://orcid.org/0000-0002-9141-8001)
- Birgit Bremer (ORCID: https://orcid.org/0000-0002-1239-6968)
- I Prinz
- Katja Steppich
- Sarina Ravens (ORCID: https://orcid.org/0000-0002-3265-6341)
- Arnaud Carpentier (ORCID: https://orcid.org/0000-0002-6994-4689)
- Rodrigo Gutierrez Jauregui (ORCID: https://orcid.org/0000-0003-3881-7721)
- Matthias Bruhn (ORCID: https://orcid.org/0009-0008-2748-4080)
- P Schröter
- Ansgar Schnieders
- Erich Freyer (ORCID: https://orcid.org/0000-0002-1715-1337)
- Heiner H. Wedemeyer (ORCID: https://orcid.org/0000-0003-2906-0480)
- Yannic C. Bartsch (ORCID: https://orcid.org/0000-0002-3844-3056)
- Vicente Almeida (ORCID: https://orcid.org/0000-0002-8821-5895)
- Sebastian Klein
- Constantin von Kaisenberg
- A Kraft
- Ulrich Kalinke
- Ayesha D Lietzau
- Ximena León-Lara
- Laura Fernández Carrera
- Carla Meineke
- Zheng Song
Institutions
- Leibniz University Hannover (DE)
- Universität Hamburg (DE)
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- German Center for Infection Research (DE)
- Helmholtz Centre for Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
Publication Details
- Journal
- Gut
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1136/gutjnl-2025-337640
- Citations
- 1
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 18.84
Funders
- Deutsches Zentrum für Infektionsforschung
- Deutsche Forschungsgemeinschaft
- Helmholtz Association