Gehring, AJ; Kennedy, PTF; Selden, C; Bertoletti, A; Sun, D; Nassal, M; ... Maini, MK; + view all Gehring, AJ; Kennedy, PTF; Selden, C; Bertoletti, A; Sun, D; Nassal, M; Nolte-'T Hoen, E; Davis, DM; Lim, SG; Wasser, S; Maini, MK; - view fewer (2007) The level of viral antigen presented by hepatocytes influences CD8 T-cell function. Journal of Virology , 81 (6) 2940 - 2949. 10.1128/JVI.02415-06.
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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-ceII antiviral efficiency against hepatotropic viruses has been linked to their capacity to produce gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). On the other hand, intrahepatic cytokine production triggers the recruitment of mononaclear 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-γ and TNF-α 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
|Title:||The level of viral antigen presented by hepatocytes influences CD8 T-cell function|
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