title: CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes.
abstract: 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)-gamma or IFN-gamma 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-alpha/beta 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.
  
  
  CONCLUSIONS
  These findings provide direct in vitro evidence at cellular and molecular levels that CD56(+) T cells may have an essential role in innate immune cell-mediated defense against HCV infection. (HEPATOLOGY 2009.).
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Joseph Stokes, Jr Research Institute at The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Shihong
authors.initials: S
authors.lastname: Wang
authors.forename: Yanjian
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000473:pathology / Q000517:prevention & control; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D019002:CD56 Antigen; D016898:Interferon-alpha; D012367:RNA, Viral; D050791:STAT Transcription Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D053612:Janus Kinases