Association of NKG2A with treatment for chronic hepatitis C virus infection

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http://www3.interscience.wiley.com/journal/123506198/abstract

Clinical & Experimental Immunology

Volume 161 Issue 2, Pages 306 - 314

Published Online: 9 Jun 2010

Journal Compilation © 2010 British Society for Immunology

ORIGINAL ARTICLE

Association of NKG2A with treatment for chronic hepatitis C virus infection

R. J. on,* A. Ettorre,* A.-M. Little † and S. I. Khakoo*

*Department of Hepatology, Division of Medicine, Imperial College, and †

Nolan Research Institute, The Royal Free Hospital, London, UK

Correspondence to S. I. Khakoo, Division of Medicine, Imperial College London,

St 's Hospital Campus, South Wharf Road, London W2 1PG, UK.

E-mail: skhakoo@...

Copyright Journal Compilation © 2010 British Society for Immunology

KEYWORDS

hepatitis C • interferon-alpha • killer cell immunoglobulin-like receptors •

natural killer cells • NKG2A

ABSTRACT

Natural killer (NK) cells are critical to the immune response to viral

infections. Their functions are controlled by receptors for major

histocompatibility complex (MHC) class I, including NKG2A and killer-cell

immunoglobulin-like receptors (KIR). In order to evaluate the role of MHC class

I receptors in the immune response to hepatitis C virus infection we have

studied patients with chronic HCV infection by multi-parameter flow cytometry

directly ex vivo. This has permitted evaluation of combinatorial expression of

activating and inhibitory receptors on single NK cells. Individuals with chronic

HCV infection had fewer CD56dim NK cells than healthy controls (4·9 ± 3·4%

versus 9·0 ± 5·9%, P < 0·05). Expression levels of the inhibitory receptor NKG2A

was up-regulated on NK cells from individuals with chronic hepatitis C virus

(HCV) (NKG2A mean fluorescence intensity 5692 ± 2032 versus 4525 ± 1646, P <

0·05). Twelve individuals were treated with pegylated interferon and ribavirin.

This resulted in a down-regulation of NKG2A expression on CD56dim NK cells.

Individuals with a sustained virological response (SVR) had greater numbers of

NKG2A-positive, KIR-negative NK cells than those without SVR (27·6 ± 9·6% NK

cells versus 17·6 ± 5·7, P < 0·02). Our data show that NKG2A expression is

dysregulated in chronic HCV infection and that NKG2A-positive NK cells are

associated with a beneficial response to pegylated interferon and ribavirin

therapy.

Accepted for publication 10 March 2010

DIGITAL OBJECT IDENTIFIER (DOI)10.1111/j.1365-2249.2010.04169

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