T-bet expression in CD8+ T cells associated with chronic hepatitis B virus infection

Virol J. 2016 Jan 25:13:14. doi: 10.1186/s12985-016-0473-y.

Abstract

Background: The mechanisms leading to virus-specific CD8+ T cell dysfuction in chronic hepatitis B virus (HBV) infection remain to be elucidated. Our study focused on the role of transcription factor T-bet in HBV infection because it is a crucial regulator of T cell immunity.

Methods: We assessed the expression of T-bet along with PD-1, IFN-γ and perforin, in HBV-specific CD8+ T cells from resolved acute hepatitis B (rAHB) patients, chronic hepatitis B (CHB) patients, as well as asymptomatic HBV carriers (ASCs). We observed dynamic changes of T-bet, PD-1, IFN-γ and perforin in acute stage and recovery stage of acute hepatitis B (AHB).

Results: Comparing with other cohorts, HBV-specific CD8+ T cells from rAHB demonstrated a superior ability in T-bet, IFN-γ and perforin expression, but an inferior ability in PD-1 expression. In the CHB group, the level of T-bet has a linear relationship with the level of PD-1, IFN-γ and HBV DNA, respectively. A lower expression of T-bet and PD-1 was observed in ASCs when compared with CHB. A higher expression of T-bet, PD-1, IFN-r and perforin was observed in acute stage when compared with the recovery stage of AHB.

Conclusions: Our results suggest that expression of T-bet may influence the function of HBV-specific CD8+ T cells and thus can be an attractive target for modulation to improve HBV-specific immunity in CHB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • DNA, Viral
  • Female
  • Flow Cytometry
  • Gene Expression
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / metabolism*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-gamma / biosynthesis
  • Male
  • Middle Aged
  • Perforin / biosynthesis
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • T-Cell Antigen Receptor Specificity / immunology
  • Viral Load

Substances

  • Biomarkers
  • DNA, Viral
  • Programmed Cell Death 1 Receptor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Perforin
  • Interferon-gamma