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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation
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Antigens, CD / biosynthesis
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Antigens, Surface / immunology*
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Antigens, Viral / immunology
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Autocrine Communication
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Cell Differentiation
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Chlorocebus aethiops
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Dendritic Cells / cytology*
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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GTP-Binding Proteins*
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Hemagglutinins, Viral / genetics
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Hemagglutinins, Viral / immunology*
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Humans
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Immune Tolerance / physiology*
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Interferon-alpha / biosynthesis
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Interleukin-4 / pharmacology
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation
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Lymphocyte Culture Test, Mixed
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Measles virus / genetics
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Measles virus / immunology*
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Measles virus / radiation effects
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Membrane Glycoproteins*
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Myxovirus Resistance Proteins
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Phytohemagglutinins / pharmacology
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Protein Biosynthesis
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / immunology
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T-Lymphocytes / immunology
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Ultraviolet Rays
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Vero Cells
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Vesicular stomatitis Indiana virus / genetics
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Vesicular stomatitis Indiana virus / immunology
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Viral Fusion Proteins / genetics
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Viral Fusion Proteins / immunology*
Substances
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Antigens, CD
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Antigens, Surface
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Antigens, Viral
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G protein, vesicular stomatitis virus
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Hemagglutinins, Viral
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Interferon-alpha
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Lipopolysaccharides
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Membrane Glycoproteins
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Myxovirus Resistance Proteins
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Phytohemagglutinins
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Recombinant Fusion Proteins
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Viral Envelope Proteins
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Viral Fusion Proteins
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hemagglutinin protein G, measles virus
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Interleukin-4
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Granulocyte-Macrophage Colony-Stimulating Factor
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GTP-Binding Proteins