title: Measles virus-induced promotion of dendritic cell maturation by soluble mediators does not overcome the immunosuppressive activity of viral glycoproteins on the cell surface.
abstract: Measles virus (MV) infection promotes maturation of dendritic cells (DC), but also interferes with DC functions, and MV renders the DC inhibitory for T cell proliferation. We now describe that MV infection triggers the release of type I IFN from monocyte-derived DC (Mo-DC) which contributes to DC maturation. There is no evidence that soluble mediators are released interfering with the stimulatory activity of uninfected DC. Since inhibition of allogeneic T cell proliferation was unaffected by a fusion inhibitory peptide (Z-fFG), MV infection of T cells did not contribute to inhibition. Allogeneic T cell proliferation depended on the percentage of DC expressing MV F/H glycoproteins within the DC population and their surface expression levels, was induced upon addition of UV-inactivated MV to a mixed lymphocyte reaction stimulated by lipopolysaccharide-matured DC, and was not induced by DC infected with a recombinant MV encoding the ectodomain of vesicular stomatitis virus G protein (MG/FV) instead of the MV glycoproteins. Similarly, DC infected with MV, but not with MG/FV inhibited mitogen-induced proliferation of T cells. Thus, a dominant inhibitory signal is delivered to T cells by the MV glycoproteins on the surface of DC overcoming positive signals by co-stimulatory molecules promoted by maturation factors released from infected DC.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Germany.
authors.forename: I M
authors.initials: IM
authors.lastname: Klagge
authors.forename: V
authors.initials: V
authors.lastname: ter Meulen
authors.forename: S
authors.initials: S
authors.lastname: Schneider-Schaulies
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D019898:Autocrine Communication; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D019204:GTP-Binding Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008459:Measles virus / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D010835:Phytohemagglutinins / Q000494:pharmacology; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D000956:Antigens, Viral; C028391:G protein, vesicular stomatitis virus; D006389:Hemagglutinins, Viral; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D010835:Phytohemagglutinins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019204:GTP-Binding Proteins