Redistribution of regulatory T-cells across the evolving stages of chronic hepatitis C

Dig Liver Dis. 2011 Oct;43(10):807-13. doi: 10.1016/j.dld.2011.04.020.

Abstract

Background: Hepatitis C virus infection frequently leads to chronic hepatitis, possibly evolving to end-stage liver disease and hepatocellular carcinoma. Regulatory T cells can affect antiviral immune response thus influencing the outcome of the disease.

Aim: To determine numeric and functional distribution of regulatory T cells expressing CD4+CD25hiFoxp3+ (T-regs) during the different stages of hepatitis C virus-related liver disease.

Methods: 90 hepatitis C viraemic patients and 50 healthy controls were included. Surface and intracellular (Foxp3) T-reg markers were evaluated by flow cytometry. Target cell proliferation and interferon-gamma production were evaluated in 37 HCV patients. In 16 cases intrahepatic distribution of Foxp3 by immuno-histochemistry was assessed.

Results: T-regs were increased in hepatitis C virus infected patients and correlated inversely with aminotransferases and directly with MELD score and disease duration. A preserved inhibitory ability of interferon-gamma production was distinctive of patients with normal aminotransferases. Circulating T-regs did not correlate with intrahepatic distribution of Foxp3.

Conclusions: In chronic hepatitis C, selective expansion of peripheral T-regs in patients with normal aminotransferases and advanced disease suggests that, though a continual low level inflammation does not prevent liver disease progression, once cirrhosis has developed it may represent an attempt to prevent immuno-mediated decompensation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • End Stage Liver Disease / blood
  • End Stage Liver Disease / immunology*
  • Female
  • Forkhead Transcription Factors / blood
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interferon-gamma / blood
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / immunology
  • Liver Neoplasms / blood
  • Liver Neoplasms / immunology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Statistics, Nonparametric
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / metabolism
  • Young Adult
  • gamma-Glutamyltransferase / blood

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interferon-gamma
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase