Differential alteration of CD56(bright) and CD56 (dim) natural killer cells in frequency, phenotype, and cytokine response in chronic hepatitis C virus infection

J Gastroenterol. 2011 Aug;46(8):1020-30. doi: 10.1007/s00535-011-0408-8. Epub 2011 May 11.

Abstract

Background: Natural killer (NK) cells play an important role in immune responses to virus infection. The cell population consists of CD56(bright) (bright-subset) and CD56(dim) (dim-subset) subsets that possess armed functions of cytokine production and cytolysis, respectively. How these subsets are involved in chronic hepatitis C virus infection (CHC) remains obscure.

Methods: We investigated the frequency, phenotype, and cytokine response of these subsets in blood from CHC patients and healthy subjects (HS).

Results: Dim-subset, but not bright-subset, showed lower frequency in the patients than in HS. Bright-subset from the patients more frequently expressed the NKG2A/CD94 inhibitory receptor than that from HS, while both subsets from the patients expressed lower levels of the NKG2D activating receptor. Both subsets from the patients displayed a significantly higher level of the signal transducer and activator of transcription (STAT) 1, compared with the HS. Upon stimulation with interferon-α, bright-subset activated less STAT4, required for interferon-γ production, and dim-subset activated more STAT1, required for cytolysis, in the patients than in HS.

Conclusions: These results indicate alterations of NK cell subsets in frequency, phenotype, and cytokine response in CHC, which might be associated with the immune pathogenesis of CHC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD56 Antigen / metabolism*
  • Cytokine-Induced Killer Cells / immunology
  • Cytokine-Induced Killer Cells / metabolism
  • Cytokines / metabolism
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Phenotype
  • STAT1 Transcription Factor / metabolism
  • STAT4 Transcription Factor / metabolism

Substances

  • CD56 Antigen
  • Cytokines
  • NK Cell Lectin-Like Receptor Subfamily K
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT4 Transcription Factor
  • STAT4 protein, human