Decreased peripheral natural killer cells activity in the immune activated stage of chronic hepatitis B

PLoS One. 2014 Feb 10;9(2):e86927. doi: 10.1371/journal.pone.0086927. eCollection 2014.

Abstract

Background & aims: The natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. In our study, we investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection.

Methods: Blood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB), including 15 patients in the immune tolerant (IT) stage, 42 patients in the immune activated (IA) stage, and 18 healthy individuals (HI). The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity.

Results: NK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (p<0.05). Patients in the IA stage of CHB had lower levels of NK cells activating receptor NKp30 and NKG2D expression, cytokine interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, as compared to patients in the IT stage and HI, respectively (p<0.05). Cytotoxicity of NK cells was lower in patients in the IA stage of CHB compared to patients in the IT stage and HI, respectively (p<0.05). The level of IFN-γ but not level of TNF-α and cytotoxicity of NK cells was inversely correlated with serum HBV load in patients with CHB. Peripheral NK cells activity did not correlate with ALT level.

Conclusion: NK cells activity was lower in CHB patients, especially in those in the IA stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Cytotoxicity, Immunologic
  • DNA, Viral / blood
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Immunity / immunology*
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Liver / pathology
  • Liver / virology
  • Lymphocyte Subsets / immunology
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Virus Replication

Substances

  • DNA, Viral
  • Receptors, Immunologic
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Alanine Transaminase

Grants and funding

This work was supported by grants from the National Science Fund of China (NSFC) (grant number 30771911), the National Key Basic Research Program of China (grant number 2009CB522502) and the National Science and Technology Major Project (grant numbers 2008ZX10002-014, 2008ZX10002-009, 2012ZX10002007-003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.