Measles virus-induced promotion of dendritic cell maturation by soluble mediators does not overcome the immunosuppressive activity of viral glycoproteins on the cell surface.
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.
Klagge
I M
IM
Institute for Virology and Immunobiology, University of Würzburg, Germany.
ter Meulen
V
V
Schneider-Schaulies
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S
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*
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