Enhanced peripheral γδT cells cytotoxicity potential in patients with HBV-associated acute-on-chronic liver failure might contribute to the disease progression

J Clin Immunol. 2012 Aug;32(4):877-85. doi: 10.1007/s10875-012-9678-z. Epub 2012 Mar 14.

Abstract

Background: The current study explored the characteristics of γδ T cells in the blood of HBV-associated acute-on-chronic liver failure (HBV-ACLF) patients and examined the relationship between γδ T cells and the clinical parameters.

Methods: Blood samples were obtained from 26 patients with HBV-ACLF, 40 patients with chronic hepatitis B virus (HBV) infection (CHBV), and 25 healthy controls (HC). The frequencies of γδ T cells, subtype Vδ1T or Vδ2T, and CD45RO(+)γδ T cells were determined using flow cytometry. Intracellular cytokine staining analysis was used to evaluate the proportion of the IFN-γ-, TNF-α-, or IL-17-producing γδ T cells, and CD107a- or granzyme B-positive γδ T cells.

Results: We found that the proportion of γδ T cells in blood samples from HBV-ACLF patients was much lower than in samples from CHBV patients or healthy controls. After stimulation with PMA and ionomycin, γδ T cells from HBV-ACLF patients produced the greatest amount of TNF-α or IL-17 among the three groups. Granzyme B- or CD107a-positive γδ T cells were significantly more frequent than in CHBV or control samples. There was a negative correlation between the percent of TNF-α(+)γδ T cells and ALT or AST levels, and between the percent of CD107a(+)γδ T cells and TBiL or DBiL levels.

Conclusions: These results suggest that γδ T cells might participate in liver injury in HBV-ACLF patients by producing increased amounts of inflammatory cytokines and/or cytotoxicity ability. These findings provide novel information regarding the pathogenesis of HBV-ACLF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cytotoxicity, Immunologic*
  • Disease Progression
  • End Stage Liver Disease / immunology*
  • End Stage Liver Disease / virology
  • Female
  • Granzymes / metabolism
  • Hepatitis B / complications
  • Hepatitis B / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / biosynthesis
  • Ionomycin / pharmacology
  • Liver Failure, Acute / immunology*
  • Liver Failure, Acute / virology
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Interleukin-17
  • Lysosomal-Associated Membrane Protein 1
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor-alpha
  • Ionomycin
  • Interferon-gamma
  • Granzymes