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Gut 57:1121-1128 doi:10.1136/gut.2007.130963
  • Hepatology

Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure

  1. L Golden-Mason1,
  2. L Madrigal-Estebas2,
  3. E McGrath1,
  4. M J Conroy2,
  5. E J Ryan1,
  6. J E Hegarty3,4,
  7. C O’Farrelly1,4,
  8. D G Doherty2
  1. 1
    Education & Research Centre, St. Vincent’s University Hospital, Dublin, Ireland
  2. 2
    Institute of Immunology & Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland
  3. 3
    National Liver Transplant Unit, St. Vincent’s University Hospital, Dublin, Ireland
  4. 4
    The Conway Institute of Biomolecular Medicine, University College, Dublin, Ireland
  1. Dr Derek G Doherty, Institute of Immunology & Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland; derek.g.doherty{at}nuim.ie
  • Revised 7 March 2008
  • Accepted 11 March 2008
  • Published Online First 27 March 2008

Abstract

Background: Natural killer (NK) cells may be impaired in patients with persistent hepatitis C virus (HCV) infection, but studies to date have yielded inconsistent findings due to patient and virus heterogeneity and difficulties obtaining appropriate controls.

Aims: To overcome these variables, we have examined numbers, phenotypes, cytotoxic activities and cytokine profiles of circulating NK cells from Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source and matched controls.

Results: Comparing 29 women who developed persistent infection with 21 who spontaneously resolved infection and 26 controls, we found that NK cell numbers were consistently lower in the persistently infected group (p = 0.02 and 0.002). This decrease was due to depletions of NK cells expressing low levels of CD56 (CD56dim NK cells; p = 0.004 and 0.0001), whilst CD56bright NK cells were expanded (p = 0.004 and 0.0001). Compared to HCV resolvers, CD56dim NK cells from persistently infected patients less frequently expressed CD16 and more frequently expressed NKG2A/C/E. These phenotypic changes did not significantly affect natural or interleukin-2-induced cytotoxicity by peripheral blood mononuclear cells against K562 and Daudi targets. Greater frequencies of CD56bright NK cells from chronic HCV patients produced interferon-γ compared with HCV responders (p = 0.05) and controls (p = 0.0001) after phorbol ester stimulation in vitro.

Conclusions: Alterations in NK subset distributions in chronic HCV infection may explain why previous reports of impaired NK cell functions were difficult to confirm. Altered NK cell functions may contribute to impaired cellular immune responses and chronicity of disease following HCV infection.

Footnotes

  • Funding: This work was supported by the Irish Health Research Board and Science Foundation, Ireland.

  • Competing interests: None.

  • Ethics approval: This study received ethics approval from the Research and Ethics Committee at St Vincent’s University Hospital, 11 December 2002, and conforms to the guidelines of the 1975 Declaration of Helsinki.