title: Role of liver-infiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Natural killer T (NKT) cells have been recently reported to concern with various lipid disorders. The role of NKT cells in the hepatic lipid disorder, nonalcoholic fatty liver disease (NAFLD), has, however, not yet been clarified. To assess the role of NKT cells in the pathogenesis of NAFLD, we analyzed the composition and function of liver-infiltrating cells isolated from liver biopsy specimens of patients with NAFLD.
  
  
  METHODS
  Specimens from 62 patients with NAFLD were studied, and 54 specimens among them reacted immunohistochemically with monoclonal antibodies against various surface markers. Moreover, using flow cytometry, we analyzed surface markers and intracytoplasmic cytokines of intrahepatic CD3+CD56+ cells in 12 patients among them.
  
  
  RESULTS
  Among the various populations of liver-infiltrating cells, only the numbers of CD56+ cells were significantly increased as NAFLD disease activity (NAFLD activity score, NAS) increased. Furthermore, expression of CD1d, a ligand for NKT cells, was also increased in NAFLD as NAS increased. Flow cytometric analysis showed that most CD56+ cells were Valpha24+ NKT cells, which produced more IFN-gamma and IL-4 as NAS increased.
  
  
  CONCLUSIONS
  Intrahepatic CD3+CD56+ NKT cells are increased in NAFLD as NAS increased. These cells may enhance disease activity through cytokine production after the recognition of lipid antigens presented with CD1d in livers of NAFLD.
authors.affiliation: Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Tajiri
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama