Measles virus suppresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells.
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.
Fugier-Vivier
I
I
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Servet-Delprat
C
C
Rivailler
P
P
Rissoan
M C
MC
Liu
Y J
YJ
Rabourdin-Combe
C
C
D017209:Apoptosis; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology / Q000473:pathology / Q000821:virology; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication
D019013:CD40 Antigens; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12