title: Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection.
abstract: OBJECTIVE
  Dendritic cells (DC), which play an essential role in the triggering of primary antiviral immune reactions, may also contribute, in some viral models, to the propagation of viral infection and the pathogenesis of viral disease. During natural infection with hepatitis C virus (HCV), the interactions between the virus and DC may contribute to viral persistence, a general feature of HCV infection.
  
  
  METHODS
  We compared the phenotypical and biological functions of monocyte-derived DC from patients with chronic hepatitis C (HCV-DC; n = 6), seronegative individuals (naive-DC; n = 8), long-term responders to antiviral therapy (LTR-DC; n = 8), and a group of patients with non-HCV-hepatic disorders (n = 11). The presence and the nature of HCV sequences during the DC cultures was assessed by reverse transcription-polymerase chain reaction and the analysis of the viral quasispecies distribution.
  
  
  RESULTS
  Although HCV-DC displayed a normal morphology, phenotype, and capacity to capture antigen, their ability to stimulate the proliferation of allogeneic T cells was dramatically impaired in comparison with naive-DC (P = 0.0013). Mixing experiments revealed that HCV-DC did not affect the proliferation of T cells induced by naive-DC. Remarkably, the allostimulatory function of LTR-DC or DC from patients with non-HCV-hepatic disorders did not show any impairment. The presence of HCV genomic sequences could be documented for 5 of 6 HCV carriers either in the cells and/or the supernatants of the DC cultures. The presence of HCV sequences was found in the DC cultures from one patient showing a dramatic allostimulation defect. For that patient, extensive analysis of the viral quasispecies distribution revealed the presence, in the DC cultures, of genomic sequences of a unique nature, distinct from those identified in the patient's mononuclear cells, serum, or liver.
  
  
  CONCLUSIONS
  Overall, these results indicate that chronic infection by HCV is associated with an allostimulatory defect of monocyte-derived DC, possibly because these cells constitute an extrahepatic reservoir for the virus. Although the exact mechanism responsible for such an alteration remains to be unraveled, our observations argue against an active immunosuppression-based mechanism.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bain
authors.forename: A
authors.initials: A
authors.lastname: Fatmi
authors.forename: F
authors.initials: F
authors.lastname: Zoulim
authors.forename: J P
authors.initials: JP
authors.lastname: Zarski
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: G
authors.initials: G
authors.lastname: Inchauspé
mesh_terms: D017502:Adenovirus E2 Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008107:Liver Diseases / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014779:Virus Replication
chemical_list: D017502:Adenovirus E2 Proteins; D022801:Complementarity Determining Regions; D004279:DNA, Viral