J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/09/813/11 $2.00
Volume 186, Number 6, September 15, 1997 813-823

Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells

By Isabelle Fugier-Vivier,^* Christine Servet-Delprat, Pierre Rivailler, Marie-Clotilde Rissoan,^* Yong-Jun Liu,^* and Chantal Rabourdin-Combe

From the ^* Laboratory for Immunological Research, Schering-Plough, Dardilly, France; and  Immunobiologie Moléculaire, Laboratoire de Biologie Cellulaire et Moléculaire de l'Ecole Normale Supérieure de Lyon, Lyon, France

Secondary infections due to a marked immunosuppression have long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. The mechanisms underlying the inhibition of cell-mediated immunity are not clearly understood but dysfunctions of monocytes as antigen-presenting cells (APC) are implicated. In this report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated monocytes, but intensively in CD40-activated DC. The interaction of MV-infected DC with T cells not only induces syncytia formation where MV undergoes massive replication, but also leads to an impairment of DC and T cell function and cell death. CD40-activated DC decrease their capacity to produce interleukin (IL) 12, and T cells are unable to proliferate in response to MV-infected DC stimulation. A massive apoptosis of both DC and T cells is observed in the MV pulsed DC-T cell cocultures. This study suggests that DC represent a major target of MV. The enhanced MV replication during DC-T cell interaction, leading to an IL-12 production decrease and the deletion of DC and T cells, may be the essential mechanism of immunosuppression induced by MV.

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• Ignatius, R., Marovich, M., Mehlhop, E., Villamide, L., Mahnke, K., Cox, W. I., Isdell, F., Frankel, S. S., Mascola, J. R., Steinman, R. M., Pope, M. (2000). Canarypox Virus-Induced Maturation of Dendritic Cells Is Mediated by Apoptotic Cell Death and Tumor Necrosis Factor Alpha Secretion. J. Virol. 74: 11329-11338 [Abstract] [Full Text]  
• Kurita-Taniguchi, M., Fukui, A., Hazeki, K., Hirano, A., Tsuji, S., Matsumoto, M., Watanabe, M., Ueda, S., Seya, T. (2000). Functional Modulation of Human Macrophages Through CD46 (Measles Virus Receptor): Production of IL-12 p40 and Nitric Oxide in Association with Recruitment of Protein-Tyrosine Phosphatase SHP-1 to CD46. J. Immunol. 165: 5143-5152 [Abstract] [Full Text]  
• Naniche, D., Yeh, A., Eto, D., Manchester, M., Friedman, R. M., Oldstone, M. B. A. (2000). Evasion of Host Defenses by Measles Virus: Wild-Type Measles Virus Infection Interferes with Induction of Alpha/Beta Interferon Production. J. Virol. 74: 7478-7484 [Abstract] [Full Text]  
• Kruse, M., Rosorius, O., Krätzer, F., Stelz, G., Kuhnt, C., Schuler, G., Hauber, J., Steinkasserer, A. (2000). Mature Dendritic Cells Infected with Herpes Simplex Virus Type 1 Exhibit Inhibited T-Cell Stimulatory Capacity. J. Virol. 74: 7127-7136 [Abstract] [Full Text]  
• Astier, A., Trescol-Biemont, M.-C., Azocar, O., Lamouille, B., Rabourdin-Combe, C. (2000). Cutting Edge: CD46, a New Costimulatory Molecule for T Cells, That Induces p120CBL and LAT Phosphorylation. J. Immunol. 164: 6091-6095 [Abstract] [Full Text]  
• d'Ostiani, C. F., Del Sero, G., Bacci, A., Montagnoli, C., Spreca, A., Mencacci, A., Ricciardi-Castagnoli, P., Romani, L. (2000). Dendritic Cells Discriminate between Yeasts and Hyphae of the Fungus Candida albicans: Implications for Initiation of T Helper Cell Immunity In Vitro and In Vivo. JEM 191: 1661-1674 [Abstract] [Full Text]  
• Servet-Delprat, C., Vidalain, P.-O., Azocar, O., Le Deist, F., Fischer, A., Rabourdin-Combe, C. (2000). Consequences of Fas-Mediated Human Dendritic Cell Apoptosis Induced by Measles Virus. J. Virol. 74: 4387-4393 [Abstract] [Full Text]  
• Zarozinski, C. C., McNally, J. M., Lohman, B. L., Daniels, K. A., Welsh, R. M. (2000). Bystander Sensitization to Activation-Induced Cell Death as a Mechanism of Virus-Induced Immune Suppression. J. Virol. 74: 3650-3658 [Abstract] [Full Text]  
• Weidmann, A., Maisner, A., Garten, W., Seufert, M., ter Meulen, V., Schneider-Schaulies, S. (2000). Proteolytic Cleavage of the Fusion Protein but Not Membrane Fusion Is Required for Measles Virus-Induced Immunosuppression In Vitro. J. Virol. 74: 1985-1993 [Abstract] [Full Text]  
• Servet-Delprat, C., Vidalain, P.-O., Bausinger, H., Manie, S., Le Deist, F., Azocar, O., Hanau, D., Fischer, A., Rabourdin-Combe, C. (2000). Measles Virus Induces Abnormal Differentiation of CD40 Ligand-Activated Human Dendritic Cells. J. Immunol. 164: 1753-1760 [Abstract] [Full Text]  
• Riegler, S., Hebart, H., Einsele, H., Brossart, P., Jahn, G., Sinzger, C. (2000). Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus. J. Gen. Virol. 81: 393-399 [Abstract] [Full Text]  
• Mrkic, B., Odermatt, B., Klein, M. A., Billeter, M. A., Pavlovic, J., Cattaneo, R. (2000). Lymphatic Dissemination and Comparative Pathology of Recombinant Measles Viruses in Genetically Modified Mice. J. Virol. 74: 1364-1372 [Abstract] [Full Text]  
• Vidalain, P.-O., Azocar, O., Lamouille, B., Astier, A., Rabourdin-Combe, C., Servet-Delprat, C. (2000). Measles Virus Induces Functional TRAIL Production by Human Dendritic Cells. J. Virol. 74: 556-559 [Abstract] [Full Text]  
• van den Broek, M., Bachmann, M. F., Kohler, G., Barner, M., Escher, R., Zinkernagel, R., Kopf, M. (2000). IL-4 and IL-10 Antagonize IL-12-Mediated Protection Against Acute Vaccinia Virus Infection with a Limited Role of IFN-{gamma} and Nitric Oxide Synthetase 2. J. Immunol. 164: 371-378 [Abstract] [Full Text]  
• Rea, D., Schagen, F. H. E., Hoeben, R. C., Mehtali, M., Havenga, M. J. E., Toes, R. E. M., Melief, C. J. M., Offringa, R. (1999). Adenoviruses Activate Human Dendritic Cells without Polarization toward a T-Helper Type 1-Inducing Subset. J. Virol. 73: 10245-10253 [Abstract] [Full Text]  

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