title: Monocyte derived dendritic cells retain their functional capacity in patients following infection with hepatitis C virus.
abstract: Studies assessing the function of monocyte derived dendritic cells (MD-DC) in individuals with hepatitis C virus (HCV) infection have shown conflicting results. Impaired MD-DC function in chronic HCV infection would have important implications both for understanding the pathogenesis of HCV infection and in the use of autologous MD-DC in vaccination strategies. We determined the allostimulatory capacity of MD-DC in the same patient before and after HCV infection. Next, the phenotype, cytokine production and allostimulatory function of immature and mature MD-DC in individuals with persistent HCV infection were compared directly with MD-DC from healthy individuals. Finally, we assessed the ability of MD-DC to prime autologous naïve peptide specific CD8+ T cells using HLA-A2 class-I tetramers. DCs retained the same allostimulatory capacity before and following the establishment of persistent HCV infection. The surface phenotype and the amount of interleukin (IL)-10 and IL-12(p70) produced during DC maturation did not differ between HCV-infected individuals and healthy controls. Mature DCs from HCV-infected individuals performed comparably in an allogeneic MLR compared with healthy individuals. Mature MD-DC from HCV-infected individuals stimulated the expansion of peptide specific naïve CD8+ T cells. MD-DC from HCV-infected and healthy individuals are phenotypically indistinguishable and perform comparably in functional assays.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: E
authors.initials: E
authors.lastname: Barnes
authors.forename: M
authors.initials: M
authors.lastname: Salio
authors.forename: V
authors.initials: V
authors.lastname: Cerundolo
authors.forename: L
authors.initials: L
authors.lastname: Francesco
authors.forename: D
authors.initials: D
authors.lastname: Pardoll
authors.forename: P
authors.initials: P
authors.lastname: Klenerman
authors.forename: A
authors.initials: A
authors.lastname: Cox
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000954:Antigens, Surface; D016753:Interleukin-10; D018664:Interleukin-12