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© The Rockefeller University Press, 0022-1007/1997/9/813/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 813-823

Articles

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

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

From the * Laboratory for Immunological Research, Schering-Plough, Dardilly, France; and {ddagger} 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.

Address correspondence to Professor Chantal Rabourdin-Combe, Immunobiologie Moléculaire, Laboratoire de Biologie cellulaire et Moléculaire de l'Ecole Normale Supérieure de Lyon, Unité mixte de Recherche UMR49, C.N.R.S./E.N.S./laboratoire associé I.N.R.A., 69364 Lyon cedex 07, France. Phone: 33-4-72-72-80-16; FAX: 33-4-72-72-86-86; E-mail: Chantal.Rabourdin-Combe{at}ens-lyon.fr

1 Abbreviations used in this paper: DC, dendritic cells; L, ligand; L+, ligand-transfected; MV, measles virus; NP, nucleoprotein; UV-MV, ultraviolet-inactivated measles virus.

I. Fugier-Vivier and C. Servet-Delprat contributed equally to this work.


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