Effects of the CCR5-Delta32 mutation on hepatitis C virus-specific immune responses in patients with haemophilia

Immunol Invest. 2009;38(1):1-13. doi: 10.1080/08820130802307294.

Abstract

In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-n32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-n32 heterozygous n = 5 and CCR5-n32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was studied. Overall IFN-gamma responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-n32 carriers (0.6 versus 0.24 SFC/10(4) PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-n32 may potentially result in subtle reduction of HCV specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.

MeSH terms

  • Adult
  • Aged
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cell Proliferation
  • Chemokines / genetics
  • Female
  • Hemophilia A / complications
  • Hemophilia A / genetics*
  • Hemophilia A / immunology*
  • Hepacivirus / immunology*
  • Hepacivirus / pathogenicity
  • Hepatitis C / complications
  • Hepatitis C / genetics*
  • Hepatitis C / immunology*
  • Hepatitis C Antigens / immunology
  • Hepatitis C Antigens / metabolism*
  • Humans
  • Immunity, Cellular / genetics
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Lymphocyte Activation / genetics
  • Male
  • Middle Aged
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism
  • Sequence Deletion*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Virulence / genetics
  • Virulence / immunology

Substances

  • Chemokines
  • Hepatitis C Antigens
  • Receptors, CCR5
  • Interferon-gamma