Hepatitis C virus-specific cellular immune responses in sustained virological responders with viral persistence in peripheral blood mononuclear cells

Liver Int. 2014 Jul;34(6):e80-8. doi: 10.1111/liv.12320. Epub 2013 Oct 16.

Abstract

Background & aims: Hepatitis C virus (HCV)-RNA detection in peripheral blood mononuclear cells (PBMCs) after recovery from HCV infection, is a type of occult HCV infection although is unclear how the viral persistence in PBMCs affects HCV-specific T-cell responses. The aim of this study was to investigate if cellular immune responses are modified by HCV persistence in PBMCs.

Methods: HCV-specific CD4(+) and CD8(+) T-cell responses against six HCV peptides, situated within the non-structural (NS) proteins NS3, NS4b and NS5b, were measured by flow cytometry-through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) and CD69 expression- in 27 sustained virological responders (SVR): 13 with and 14 without occult HCV infection in PBMCs, detected by strand-specific real-time PCR. Ten healthy individuals and 14 chronically infected patients with viraemia, were included as controls.

Results: SVR without occult infection showed a higher percentage of activated CD4(+) cells against peptides belonging to NS3 (p124, p153) and NS5b (p257, p294), activated CD8(+) cells against NS3 (p124, p153, p158) and NS5b-p294, as well as an elevated percentage of CD4(+) cells releasing IFN-γ + IL-4 against NS3-p153, and by CD8(+) cells against NS3 (p124, p153). SVR without occult infection showed a higher percentage of activation and release of IFN-γ + IL-4 by both cell subpopulations than the two group of controls, in contrast to SVR with occult infection.

Conclusion: The lower HCV-specific T-cell response found in SVR with occult infection indicates that the immune response may be impaired when the virus persists in PBMCs.

Keywords: T-cell response; flow cytometry; occult HCV infection; peripheral blood mononuclear cells; real-time PCR; sustained virological responders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Female
  • Flow Cytometry
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • RNA, Viral / blood
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Viral Nonstructural Proteins / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antiviral Agents
  • Biomarkers
  • CD69 antigen
  • IFNG protein, human
  • IL4 protein, human
  • Lectins, C-Type
  • NS3 protein, hepatitis C virus
  • NS4B protein, flavivirus
  • Peptide Fragments
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Interleukin-4
  • Interferon-gamma
  • NS-5 protein, hepatitis C virus