Factors Contributing To Immune-Enhanced Disease In The Pathogenesis of RSV

呼吸道合胞病毒(RSV)感染是幼儿呼吸道感染的主要原因，在美国每年导致12万人住院治疗。20世纪60年代初的一次疫苗试验失败的历史阻碍了RSV疫苗的开发，在那次试验中，接种疫苗的儿童没有受到保护，不会受到随后的自然感染，而是经历了更严重的疾病。随后在动物模型和人类受试者中的实验表明，严重RSV疾病的发生与病毒特异性Th2、CD4T细胞的诱导以及嗜酸性粒细胞的招募和脱颗粒有关。RSV的G糖蛋白和含有明胶等佐剂的灭活病毒疫苗可诱导与疫苗增强型疾病综合征相关的这些类型的免疫反应。 树突状细胞是处理抗原和启动免疫反应的重要细胞。了解它们与RSV的相互作用可能揭示自然RSV感染诱导相对短暂的免疫的原因。CD4T细胞可以影响和调节包括CD8T细胞在内的其他免疫效应物的功能。除了Th2CD4T细胞在上述RSV发病机制中的潜在作用外，T调节细胞还具有在RSV免疫和发病机制中可能重要的特性。

Respiratory syncytial virus (RSV) infection is the primary cause of respiratory infection in young children, causing >120,000 hospitalizations in the US annually. RSV vaccine development has been hampered by the history of a failed vaccine trial in the early 1960s in which vaccinated children were not protected against subsequent natural infection but rather experienced more severe disease. Subsequent experiments in animal models and human subjects suggest the occurrence of severe RSV disease correlates with the induction of virus-specific Th2 CD4 T cells and eosinophil recruitment and degranulation. The G glycoprotein of RSV and killed virus vaccines containing adjuvants such as alum induce these types of immune responses associated with the vaccine-enhanced disease syndrome. Dendritic cells are important for processing antigen and initiating immune responses. Understanding their interaction with RSV may reveal the reasons for relatively short-lived immunity induced by natural RSV infection. CD4 T cells can influence and regulate the function of other immune effectors including CD8 T cells. In addition to the potential role of Th2 CD4 T cells in RSV pathogenesis as mentioned above, T regulatory cells have properties that suggest they may be important in RSV immunity and pathogenesis.