title: Accumulation of Intrahepatic TNF-α-Producing NKp44+ NK Cells Correlates With Liver Fibrosis and Viral Load in Chronic HCV Infection.
abstract: In the setting of chronic hepatitis C virus (HCV) infection, changes in natural killer (NK) cells have been shown to reflect activation in response to virus stimulation. The contribution of individual natural cytotoxicity receptors to HCV infection remains to be clarified. NKp44 is the sole specific natural cytotoxicity receptor expressed only on activated NK cells.In this study, peripheral blood and liver NK-cell subsets were purified from 31 patients with chronic C hepatitis or nonalcoholic steatohepatitis, and then characterized by flow cytometry. Their polyfunctional activity was determined by expression of the CD107a degranulation marker, together with intracellular cytokine production.Unlike the patients with nonalcoholic steatohepatitis, patients with chronic HCV infection had a higher frequency of NKp44 NK cells in the liver than in their peripheral blood (P < 0.0001). Intrahepatic NKp44 NK cells from HCV individuals produced higher levels of tumor necrosis factor-α than did NKp44 NK cells (P = 0.0011). Importantly, the frequency of intrahepatic NKp44 NK cells was correlated with both HCV-RNA levels (P = 0.0234) and stage of fibrosis (P = 0.0003).Our findings suggest that the accumulation of intrahepatic tumor necrosis factor-α-producing NKp44 resident NK cells play a role in the liver damage associated with chronic HCV infection.
authors.affiliation: From the Sorbonne Universités (IN, OL, CP, VB, PD, VV), UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris; Univ Paris Diderot (ML), INSERM UMR 1149, CRI Paris Montmartre, Clichy; AP-HP (PB), Service d'Anatomie Pathologique; and AP-HP (TA, PM), Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nel
authors.forename: Olivier
authors.initials: O
authors.lastname: Lucar
authors.forename: Caroline
authors.initials: C
authors.lastname: Petitdemange
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.forename: Martine
authors.initials: M
authors.lastname: Lapalus
authors.forename: Pierre
authors.initials: P
authors.lastname: Bédossa
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000097:blood*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D014409:Tumor Necrosis Factor-alpha