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 a ssociated 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 thi s report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated mo nocytes, but intensively in CD40-activated DC. The interaction of MV-i nfected DC with T cells not only induces syncytia formation where MV u ndergoes massive replication, but also leads to an impairment of DC an d T cell function and cell death. CD40-activated DC decrease their cap acity to produce interleukin (IL) 12, and T cells are unable to prolif erate in response to MV-infected DC stimulation. A massive apoptosis o f both DC and T cells is observed in the MV pulsed DC-T cell coculture s. This study suggests that DC represent a major target of MV. The enh anced 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 es sential mechanism of immunosuppression induced by MV.