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The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function

The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function,10.1128/JVI.02415-06,Journal of Virology,Adam J. Gehring,Dianxing S

The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function   (Citations: 18)
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CD8 T cells exert their antiviral function through cytokines and lysis of infected cells. Because hepatocytes are susceptible to noncytolytic mechanisms of viral clearance, CD8 T-cell antiviral efficiency against hepato- tropic viruses has been linked to their capacity to produce gamma interferon (IFN-) and tumor necrosis factor alpha (TNF-). 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- and TNF- production in virus-specific CD8 T cells, while limiting amounts of viral antigen, both in hepatocyte-like cells and naturally infected human hepatocytes, preferentially stim- ulated 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.
Journal: Journal of Virology - J VIROL , vol. 81, no. 6, pp. 2940-2949, 2007
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