Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment.

Abstract

Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment-naïve patients who underwent treatment with pegylated IFN-α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56(bright) CD16(+/-) cell populations, increased CD56(dull) CD16(+) NK cell proportions, and lower expression of NKp30, DNAM-1, and CD85j. Similarly, reduced NK cell IFN-γ production but increased degranulation was observed among nonresponding (NR) patients. After treatment, CD56(bright) CD16(+/-) NK cell numbers increased in both SVR and NR patients, with a parallel significant increase in activating NKp30 molecule densities in SVR patients only. In vitro experiments using purified NK cells in the presence of rIL-2 and IFN-α confirmed upregulation of NKp30 and also of NKp46 and DNAM-1 in patients with subsequent SVR. Thus, differences in patient NK cell receptor expression and modulation during chronic HCV-1 infection are associated with subsequent outcome of standard treatment. Individual activating receptor expression/function integrates with KIR:HLA genotype carriage to determine the clearance of HCV infection upon treatment.

• Authors: Federica Bozzano, Antonino Picciotto, Paola Costa, Francesco Marras, Valentina Fazio, Ivan Hirsch, Daniel Olive, Lorenzo Moretta, Andrea De Maria
• Journal: European journal of immunology (Eur J Immunol) Vol. 41 Issue 10 Pg. 2905-14 (Oct 2011) ISSN: 1521-4141 [Electronic] Germany
• PMID: 21695691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• Antiviral Agents
• CD226 antigen
• CD56 Antigen
• Interferon-alpha
• LILRB1 protein, human
• Leukocyte Immunoglobulin-like Receptor B1
• NCR1 protein, human
• NCR3 protein, human
• Natural Cytotoxicity Triggering Receptor 1
• Natural Cytotoxicity Triggering Receptor 3
• Receptors, IgG
• Receptors, Immunologic
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Adult
• Aged
• Antigens, CD (biosynthesis)
• Antigens, Differentiation, T-Lymphocyte (metabolism)
• Antiviral Agents (therapeutic use)
• CD56 Antigen (biosynthesis)
• Drug Therapy, Combination
• Female
• Hepacivirus (immunology)
• Hepatitis C, Chronic (drug therapy, immunology, virology)
• Humans
• Interferon-alpha (therapeutic use)
• Killer Cells, Natural (immunology, metabolism)
• Leukocyte Immunoglobulin-like Receptor B1
• Male
• Middle Aged
• Natural Cytotoxicity Triggering Receptor 1 (metabolism)
• Natural Cytotoxicity Triggering Receptor 3 (metabolism)
• Polyethylene Glycols (therapeutic use)
• Receptors, IgG (biosynthesis)
• Receptors, Immunologic (biosynthesis)
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Treatment Outcome
• Viremia (immunology)