title: Effects of the CCR5-Delta32 mutation on hepatitis C virus-specific immune responses in patients with haemophilia.
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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Germany.
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.forename: Rainer P
authors.initials: RP
authors.lastname: Woitas
authors.forename: Agathe
authors.initials: A
authors.lastname: Iwan
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Georg
authors.initials: G
authors.lastname: Feldmann
authors.forename: Jurgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics; D005260:Female; D006467:Hemophilia A / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D018925:Chemokines; D018936:Hepatitis C Antigens; D019713:Receptors, CCR5; D007371:Interferon-gamma