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NKp46(High) expression defines a NK cell subset that is potentially involved in control of HCV replication and modulation of liver fibrosis.
MedLine Citation:
PMID:  22532190     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by a multitude of receptors, including activating NKp46 receptor. However, reports on NKp46 in hepatitis C are controversial. Therefore, we investigated hepatic recruitment and function of NKp46(+) NK cells considering differential surface expression of NKp46 resulting in NKp46(High) and NKp46(Dim) subsets. METHODS: Intra- and extra-hepatic NK cell subsets from HCV-infected patients were characterized by flow cytometry. Cytotoxic activity and IFN-γ secretion were studied using K-562, P815, and primary hepatic stellate cells as targets. Anti-HCV activity of NK cell subsets was studied using the replicon system. RESULTS: Density of NKp46 surface expression clearly segregated NKp46(Dim) and NKp46(High) subsets, which differed significantly with respect to co-expression of maturation markers and NK cell receptors. More importantly, NKp46(High) NK cells showed a higher cytolytic activity and stronger IFN-γ secretion than NKp46(Dim) NK cells. Accordingly, NKp46(High) NK cells efficiently blocked HCV replication in vitro. Blocking experiments confirmed an important role for the NKp46 receptor.Furthermore, we found an intra-hepatic accumulation of NKp46(High) NK cells. Of note, high cytolytic activity of NKp46(High) NK cells was also confirmed in the intra-hepatic NK cell population and the frequency of intra-hepatic NKp46(High) NK cells was inversely correlated with HCV-RNA levels and fibrosis stage. CONCLUSIONS: Here, we show that NKp46(High) expression defines a specific NK cell subset that may be involved in both suppression of HCV replication and HCV-associated liver damage underpinning the role of NK cells in immunopathogenesis of HCV. (HEPATOLOGY 2012.).
Authors:
Benjamin Krämer; Christian Körner; Moritz Kebschull; Andreas Glässner; Marianne Eisenhardt; Hans Dieter Nischalke; Michael Alexander; Tilman Sauerbruch; Ulrich Spengler; Jacob Nattermann
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-24
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
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