Fugier-Vivier I, Servet-Delprat C, Rivailler P, Rissoan M C, Liu Y J, Rabourdin-Combe C
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
J Exp Med. 1997 Sep 15;186(6):813-23. doi: 10.1084/jem.186.6.813.
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.
长期以来，因显著免疫抑制导致的继发感染一直被认为是与急性麻疹相关的高发病率和死亡率的主要原因。细胞介导免疫抑制的潜在机制尚不清楚，但单核细胞作为抗原呈递细胞（APC）的功能障碍与之有关。在本报告中，我们证明麻疹病毒（MV）在静息树突状细胞（DC）中的复制能力较弱，与脂多糖激活的单核细胞情况类似，但在CD40激活的DC中复制强烈。感染MV的DC与T细胞相互作用不仅会诱导合胞体形成，使MV大量复制，还会导致DC和T细胞功能受损以及细胞死亡。CD40激活的DC产生白细胞介素（IL）-12的能力下降，并且T细胞在受到感染MV的DC刺激时无法增殖。在MV刺激的DC-T细胞共培养物中观察到DC和T细胞大量凋亡。本研究表明DC是MV的主要靶标。DC-T细胞相互作用期间MV复制增强，导致IL-12产生减少以及DC和T细胞缺失，可能是MV诱导免疫抑制的关键机制。
