{
  "abstract": "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 A distinct CD16 + γδ T cell subset inversely correlated with hepatitis B core-related antigen (HBcrAg), a surrogate of intrahepatic viral replication. CD16+ γδ T cells displayed a cytotoxic signature, whereas CD16⁻ cells showed inflammatory, non-cytotoxic profiles. On hepatitis B surface antigen-specific antibody stimulation, CD16+ γδ T cells mounted potent ADCC responses, mainly mediated by Vδ2+ cells expressing the activating receptor CD226, while Vδ1+ cells preferentially expressed the inhibitory receptor TIGIT. Cytotoxic CD16+ Vδ2+ γδ T cells were present in both blood and liver. CD16+ 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 CD16 + 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": [
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Paulina E Schröter"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Katja Steppich"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Laura Fernández Carrera"
    },
    {
      "affiliations": [
        "Institute of Immunology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Zheng Song"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "CAIMed - Center for AI in Medicine, Leibniz University Hannover and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Sebastian Klein"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Roni Souleiman"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Melanie Urbanek-Quaing"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Ayesha D Lietzau"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Ansgar Schnieders"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Erich Freyer"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Birgit Bremer"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Institute of Immunology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Ximena León-Lara"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Institute of Immunology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Vicente Almeida"
    },
    {
      "affiliations": [
        "Institute of Immunology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Rodrigo Gutierrez Jauregui"
    },
    {
      "affiliations": [
        "Department of Obstetrics, Gynecology, and Reproductive Medicine, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Constantin Von Kaisenberg"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Matthias Bruhn"
    },
    {
      "affiliations": [
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Carla Meineke"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Ulrich Kalinke"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany"
      ],
      "name": "Heiner Wedemeyer"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Institute of Immunology, Hannover Medical School, Hannover, Germany",
        "Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"
      ],
      "name": "Immo Prinz"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Institute of Immunology, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Sarina Ravens"
    },
    {
      "affiliations": [
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Arnaud Carpentier"
    },
    {
      "affiliations": [
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Yannic Christoph Bartsch"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Anke R M Kraft"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany",
        "Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany",
        "TWINCORE, Centre of Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School, Hannover, Germany",
        "CAIMed - Center for AI in Medicine, Leibniz University Hannover and Hannover Medical School, Hannover, Germany"
      ],
      "name": "Markus Cornberg"
    }
  ],
  "title": "CD16+ γδ T cells mediate antibody-dependent cellular cytotoxicity and associate with viral control in chronic hepatitis B virus infection",
  "uid": "d773a541-01df-546e-97fb-f8b76c0a358b"
}