Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+natural killer-like T cells in patients with chronic hepatitis B

Tissue Antigens. 2014 Feb;83(2):76-81. doi: 10.1111/tan.12278. Epub 2014 Jan 7.

Abstract

Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+ natural killer like T (NKT-like) cells in chronic hepatitis B (CHB) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 CHB patients and 60 healthy controls. Tim-3+CD14+ cells and Tim-3+CD3+CD16/CD56+ cells were analyzed by flow cytometry. Results showed that expression of Tim-3 was significantly increased on both the monocytes and NKT-like cells in CHB patients than in controls (P = 0.002 and P < 0.001, respectively). Tim-3 levels on monocytes and NKT-like cells were further upregulated in patients with acute-on-chronic liver failure (ACLF). In addition, we assessed the correlation of Tim-3 expression with levels of alanine aminotransferase (ALT) and tumor necrosis factor alpha (TNF-α). Data revealed that Tim-3 expression on both monocytes and NKT-like cells was positively correlated with level of ALT (r = 0.59, P < 0.001, and r = 0.60, P < 0.001, respectively), whereas Tim-3 expression on NKT-like cells was negatively correlated with serum level of TNF-α (r = -0.54, P < 0.001) in CHB patients. Our results suggest that Tim-3 may play important roles in the pathogenesis of CHB.

Keywords: Tim-3; acute-on-chronic liver failure; chronic hepatitis B; monocyte; natural killer-like T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / genetics
  • Alanine Transaminase / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • CD56 Antigen / genetics
  • CD56 Antigen / immunology
  • Case-Control Studies
  • End Stage Liver Disease / etiology
  • End Stage Liver Disease / genetics*
  • End Stage Liver Disease / immunology
  • End Stage Liver Disease / virology
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gene Expression*
  • Hepatitis A Virus Cellular Receptor 2
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Immune Tolerance
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / virology
  • Liver Failure, Acute / etiology
  • Liver Failure, Acute / genetics*
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / virology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Monocytes / metabolism*
  • Monocytes / virology
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CD3 Complex
  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • NCAM1 protein, human
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Alanine Transaminase