HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) All Versions of this Article: gut.2005.076463v1 55/6/869    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nattermann, J Articles by Spengler, U Search for Related Content PubMed PubMed Citation Articles by Nattermann, J Articles by Spengler, U

Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis C

Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universitaet, Bonn, Germany

Correspondence to:
Correspondence to:
Dr J Nattermann
Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universitaet, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany; Jacob.Nattermann{at}ukb.uni-bonn.de

Introduction: Impaired activity of natural killer (NK) cells has been proposed as a mechanism contributing to viral persistence in hepatitis C virus (HCV) infection. As the function of NK cells is primarily regulated by NK cell receptors (NKR), we analysed whether decreased NK cell function in hepatitis C may be related to dysregulated NKR expression.

Patients and methods: Expression of NK cell was analysed by flow cytometry on lymphocytes from HCV(+) subjects (n = 30), patients who became HCV(–) after antiviral therapy (n = 10), healthy individuals (n = 10), and hepatitis B virus (HBV) infected patients (n = 9). Cytolytic function of lymphocytes was studied in a redirected lysis assay and in a standard ⁵¹chromium release cytotoxicity assay, respectively.

Results: In patients with chronic hepatitis C, we found a significantly reduced proportion of NKp46 and NKp30 expressing NK cells compared with healthy and HBV infected subjects. Low expression of natural cytotoxicity receptor (NCR) was also confirmed in in vitro activated NK cell populations derived from HCV patients compared with uninfected donors. In contrast, patients who cleared HCV under antiviral therapy showed normal expression of NKp44, NKp30, and NKp46. Reduced NCR expression in chronic hepatitis C was associated with a parallel decrease in NCR mediated target cell killing. Furthermore, we found a significantly increased proportion of NKG2A expressing NK cells and CD8+ T cells in HCV positive patients, resulting in a reduced cytolytic activity against cells incubated with the HLA-E stabilising peptide HCV core_35–44.

Conclusion: The present study indicates that defective expression of NKR represents a novel mechanism contributing to impaired function of NK cells and CD8+ T cells in chronic hepatitis C.

Abbreviations: HCV, hepatitis C virus; HBV, hepatitis B virus; NK, natural killer; NKR, NK cell receptors; NCR, natural cytotoxicity receptors; HIV, immunodeficiency virus; MHC, major histocompatibility complex class; TCR, T cell receptor; rIL-2, recombinant interleukin 2; TGF-ß, transforming growth factor ß

Keywords: hepatitis C virus; natural killer cell receptors; HLA-E; natural killer cells; CD8+ T cells

This article has been cited by other articles:

				L Golden-Mason, L Madrigal-Estebas, E McGrath, M J Conroy, E J Ryan, J E Hegarty, C O'Farrelly, and D G Doherty Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure Gut, August 1, 2008; 57(8): 1121 - 1128. [Abstract] [Full Text] [PDF]

				B. Majumder, N. J. Venkatachari, S. O'Leary, and V. Ayyavoo Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells J. Virol., July 15, 2008; 82(14): 7189 - 7200. [Abstract] [Full Text] [PDF]

				H. Harlin, M. Hanson, C. C. Johansson, D. Sakurai, I. Poschke, H. Norell, K.-J. Malmberg, and R. Kiessling The CD16 CD56bright NK Cell Subset Is Resistant to Reactive Oxygen Species Produced by Activated Granulocytes and Has Higher Antioxidative Capacity Than the CD16+CD56dim Subset J. Immunol., October 1, 2007; 179(7): 4513 - 4519. [Abstract] [Full Text] [PDF]

				L. Golden-Mason, N. Castelblanco, C. O'Farrelly, and H. R. Rosen Phenotypic and Functional Changes of Cytotoxic CD56pos Natural T Cells Determine Outcome of Acute Hepatitis C Virus Infection J. Virol., September 1, 2007; 81(17): 9292 - 9298. [Abstract] [Full Text] [PDF]