CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes

✍ Scribed by Li Ye; Xu Wang; Shihong Wang; Yanjian Wang; Li Song; Wei Hou; Lin Zhou; He Li; Wenzhe Ho

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 766 KB
• Volume: 49
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22715

✦ Synopsis

CD56 ؉ T cells are abundant in liver and play an important role in defense against viral infections. However, the role of CD56 ؉ T cells in control of hepatitis C virus (HCV) infection remains to be determined. We investigated the noncytolytic anti-HCV activity of primary CD56 ؉ T cells in human hepatocytes. When HCV Japanese fulminant hepatitis-1 (JFH-1)-infected hepatocytes were co-cultured with CD56 ؉ T cells or incubated in media conditioned with CD56 ؉ T cell culture supernatants (SN), HCV infectivity and replication were significantly inhibited. The antibodies to interferon (IFN)-␥ or IFN-␥ receptor could largely block CD56 ؉ T cell-mediated anti-HCV activity. Investigation of mechanism(s) responsible for CD56 ؉ T cell-mediated noncytolytic anti-HCV activity showed that CD56 ؉ T SN activated the multiple elements of janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and enhanced the expression of IFN regulatory factors (IRFs) 1, 3, 7, 8, and 9, resulting in the induction of endogenous IFN-␣/␤ expression in hepatocytes. Moreover, CD56 ؉ T SN treatment inhibited the expression of HCV-supportive micro RNA (miRNA)-122 and enhanced the levels of anti-HCV miRNA-196a in human hepatocytes. Conclusion: These findings provide direct in vitro evidence at cellular and molecular levels that CD56 ؉ T cells may have an essential role in innate immune cellmediated defense against HCV infection. (HEPATOLOGY 2009;49:753-762.)

C D56 ϩ T cells are a subset of human T lymphocytes that express the cell-surface molecular, CD56, which is typically expressed by natural killer cells. 1,2 CD56 ϩ T cells express both natural killer and T cells markers; therefore, they functionally display properties of both natural killer cells and T cells. Unlike classical T cells, CD56 ϩ T cells possess the ability to rap-