{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:00:17Z","timestamp":1765609217093,"version":"3.30.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4475,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or <jats:italic toggle=\"yes\">in vitro<\/jats:italic> model has hindered our understanding of the host T\u2013cell\/HCV interaction. Our aim was to develop an <jats:italic toggle=\"yes\">in vitro<\/jats:italic> model to study the mechanisms of HCV\u2013specific T\u2013cell\u2013mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I\u2013matched subject. CD8<jats:sup>+<\/jats:sup> T cells were expanded with 2 HCV\u2013specific\/HLA\u2013restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with <jats:sup>51<\/jats:sup>Cr. After a 48\u2013hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti\u2013interferon gamma (IFN\u2013\u03b3), anti\u2013tumor necrosis factor \u03b1 (TNF\u2013\u03b1), and anti\u2013FasL. Cytolytic activity was measured by <jats:sup>51<\/jats:sup>Cr release. HCV replicon cells express homozygous HLA\u2013A11 alleles and present HCV nonstructural proteins. HCV\u2013specific expansion of CD8<jats:sup>+<\/jats:sup> cells led to a 10\u2013fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T\u2013cell binding, suggesting cytokine\u2013mediated antiviral activity. The CD8<jats:sup>+<\/jats:sup> antiviral effect was markedly reduced by blocking either IFN\u2013\u03b3 or FasL but was unaffected by blocking TNF\u2013\u03b1. In conclusion, HCV\u2013specific CD8<jats:sup>+<\/jats:sup> cells inhibit viral RNA replication by cytokine\u2013mediated and direct cytolytic effects. This T\u2013cell\/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV\u2013infected hepatocytes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50207","type":"journal-article","created":{"date-parts":[[2003,5,28]],"date-time":"2003-05-28T22:17:49Z","timestamp":1054160269000},"page":"1335-1342","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":38,"title":["Cd8+ T\u2013Cell Interaction With Hcv Replicon Cells: Evidence for Both Cytokine\u2013 and Cell\u2013Mediated Antiviral 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