Effect of antiviral treatment of chronic hepatitis C on the frequency of regulatory T cells, T-cell activation, and serum levels of TGF-beta

APMIS. 2016 Aug;124(8):711-8. doi: 10.1111/apm.12561. Epub 2016 Jun 16.

Abstract

The aim was to analyze T-regulatory cells (Tregs), activated CD8(+) T cells, and transforming growth factor-beta (TGF)-β in hepatitis C patients. We enrolled 31 patients with chronic genotype 1 hepatitis C virus (HCV) infection, 30 seropositive persons with spontaneous HCV elimination, and 23 healthy volunteers. The patients were examined at the beginning of the interferon-alpha (IFN-α)-based therapy (baseline) and at weeks 4 (W4) and 12 (W12) of the therapy. The percentage of Tregs and the expression of activation markers CD38 and HLA-DR on CD8(+) T cells were analyzed in the peripheral blood by flow cytometry. Serum levels of TGF-β were measured in a multiplex assay using flow cytometry. The percentage of Tregs in patients was higher than in controls and seropositive persons. Similarly, the percentage of CD8(+) T cells expressing CD38 and HLA-DR was higher in patients compared with controls and seropositive persons. Chronic HCV infection is associated with elevated circulating Tregs and activated CD8(+) T cells. During IFN-α-based therapy these cells gradually increase, whereas TGF-β serum levels decrease.

Keywords: CD38; Hepatitis C virus; interferon; regulatory T cells; transforming growth factor-beta.

MeSH terms

  • ADP-ribosyl Cyclase 1 / analysis
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Flow Cytometry
  • Genotype
  • HLA-DR Antigens / analysis
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunophenotyping
  • Interferon-alpha / therapeutic use
  • Lymphocyte Activation*
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Protease Inhibitors / therapeutic use
  • Ribavirin / therapeutic use
  • Serum / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / blood*
  • Young Adult

Substances

  • Antiviral Agents
  • HLA-DR Antigens
  • Interferon-alpha
  • Membrane Glycoproteins
  • Protease Inhibitors
  • Transforming Growth Factor beta
  • Ribavirin
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1