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

Federica Bozzano, Antonino Picciotto, Paola Costa, Francesco Marras, Valentina Fazio, Ivan Hirsch, Daniel Olive, Lorenzo Moretta, Andrea de Maria

Research output: Contribution to journalArticle

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 brightCD16 +/- cell populations, increased CD56 dullCD16 + 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 brightCD16 +/- 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.

Original languageEnglish
Pages (from-to)2905-2914
Number of pages10
JournalEuropean Journal of Immunology
Volume41
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • HCV
  • IFN-α
  • NK cells
  • NKp30
  • Treatment

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment'. Together they form a unique fingerprint.

Cite this