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Because hepatocytes are susceptible to noncytolytic mechanisms of viral clearance, CD8 T-cell antiviral efficiency against hepatotropic viruses has been linked to their capacity to produce gamma interferon (IFN-\u03b3) and tumor necrosis factor alpha (TNF-\u03b1). On the other hand, intrahepatic cytokine production triggers the recruitment of mononuclear cells, which sustain acute and chronic liver damage. Using virus-specific CD8 T cells and human hepatocytes, we analyzed the modulation of virus-specific CD8 T-cell function after recognition peptide-pulsed or virally infected hepatocytes. We observed that hepatocyte antigen presentation was generally inefficient, and the quantity of viral antigen strongly influenced CD8 T-cell antiviral function. High levels of hepatitis B virus production induced robust IFN-\u03b3 and TNF-\u03b1 production in virus-specific CD8 T cells, while limiting amounts of viral antigen, both in hepatocyte-like cells and naturally infected human hepatocytes, preferentially stimulated CD8 T-cell degranulation. Our data document a mechanism where virus-specific CD8 T-cell function is influenced by the quantity of virus produced within hepatocytes.<\/jats:p>","DOI":"10.1128\/jvi.02415-06","type":"journal-article","created":{"date-parts":[[2007,1,4]],"date-time":"2007-01-04T06:28:28Z","timestamp":1167892108000},"page":"2940-2949","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function"],"prefix":"10.1128","volume":"81","author":[{"given":"Adam J.","family":"Gehring","sequence":"first","affiliation":[{"name":"UCL Institute of Hepatology, Royal Free and University College Medical School, London, United Kingdom"},{"name":"Center for Molecular Medicine, Agency for Science Technology and Research, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianxing","family":"Sun","sequence":"additional","affiliation":[{"name":"Internal Medicine II and Molecular Biology, University Hospital Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T. 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