title: Functional Behavior of NKp46-Positive Intrahepatic Natural Killer Cells Against Hepatitis C Virus Reinfection After Liver Transplantation.
abstract: BACKGROUND
  NKp46 expression in natural killer (NK) cells has recently been shown to affect the responsiveness to antiviral treatment in hepatitis C virus (HCV)-infected patients. However, the density of NKp46 on intrahepatic NK cells is remarkably higher than that on peripherally circulating NK cells, whereas the biophylactic function of intrahepatic NK cells against HCV reinfection remains unclear.
  
  
  METHODS
  We analyzed the phenotypic and functional properties of intrahepatic NK cells using mononuclear cells extracted from ex vivo liver perfusates from living liver transplantation donors. To investigate the role of intrahepatic NK cells in relation to HCV infection, we evaluated posttransplant HCV load kinetics in HCV-related patients.
  
  
  RESULTS
  Intrahepatic NK cells from healthy donors showed a distinctive phenotype even in each of the CD56 and CD56 fractions compared with peripheral blood NK cells. In the assays using a Huh7-HCV replicon system, anti-HCV activity was induced via recognition of the NK cell receptors, including NKp46, NKp30, and NKG2D, which was demonstrated by the use of monoclonal antibodies that neutralized neutralizing molecules. Unexpectedly, the density of NKp46 on intrahepatic NK cells varied considerably among individuals, allowing us to demonstrate that HCV reload in the early posttransplant period was delayed in recipients of liver allografts containing a higher proportion of NKp46 NK cells.
  
  
  CONCLUSIONS
  Intrahepatic NKp46 NK cells exhibited anti-HCV activity via cell-to-cell contact. The variation of the NKp46 proportion in individuals could be attributed to the diversity of HCV resistance observed in these individuals, which possibly reflects the clinical outcome of infection in patients.
authors.affiliation: 1 Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. 2 Gastroenterology and Metabolism, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanimine
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Abe
authors.forename: Jinlian
authors.initials: J
authors.lastname: Piao
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
mesh_terms: D000328:Adult; D064591:Allografts; D000998:Antiviral Agents / Q000627:therapeutic use; D019002:CD56 Antigen / Q000276:immunology; D002450:Cell Communication; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000097:blood; D058625:End Stage Liver Disease / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007700:Kinetics; D008099:Liver / Q000276:immunology* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000097:blood / Q000276:immunology*; D010641:Phenotype; D012008:Recurrence; D016896:Treatment Outcome; D019562:Viral Load; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D019002:CD56 Antigen; D004279:DNA, Viral; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1