Measles virus exploits dendritic cells to suppress CD4+ T-cell proliferation via expression of surface viral glycoproteins independently of T-cell trans-infection.
Dendritic cells (DC) have been proposed to play a pivotal role in transient immune suppression induced by measles virus (MV) infection. In the present study, we show that DC-induced suppression of T-cell proliferation was not mediated by IL-10 or IFNalpha/beta, which are released following infection of DC, but required cell contacts between MV-infected DC and T cells. Human sera containing neutralizing anti-MV antibodies, as well as anti-MV hemagglutinin (HA) or fusion protein (F) mAbs, were found (i) to reverse suppression and (ii) to restore DC allostimulatory capacity. Interestingly, DC-induced T-cell suppression was associated with both phenotypic and functional DC maturation, as demonstrated by IL-12 production and chemotaxis to MIP-3beta. These data suggest that MV infection turns on the maturation program of DC allowing migration to draining lymph nodes, where potent T-cell immune suppression might be achieved via cell surface expression of HA and F glycoproteins, independently of T cell trans-infection.
Dubois
B
B
INSERM U404 Immunité et Vaccination, IFR 74, CERVI, Bâtiment Institut Pasteur, Lyon, France.
Lamy
P J
PJ
Chemin
K
K
Lachaux
A
A
Kaiserlian
D
D
D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015726:Giant Cells / Q000821:virology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006389:Hemagglutinins, Viral / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008459:Measles virus / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D021122:Protein Subunits; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014466:Ultraviolet Rays; D014760:Viral Fusion Proteins / Q000096:biosynthesis / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus; D016753:Interleukin-10; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor