Wijburg O L, DiNatale S, Vadolas J, van Rooijen N, Strugnell R A
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
J Virol. 1997 Dec;71(12):9450-7. doi: 10.1128/JVI.71.12.9450-9457.1997.
Virus-specific cytotoxic T lymphocytes (CTL) are thought to be responsible for the eradication of respiratory influenza virus infections by direct cytolysis of virus-infected epithelial cells. In this study, we provide evidence for a role for alveolar macrophages (AM) in the regulation of pulmonary virus-specific CTL responses. Prior to infection with influenza virus, AM were selectively eliminated in vivo with a liposome-mediated depletion technique, and virus-specific CTL activities of lung and mediastinal lymph node (MLN) cells were assayed ex vivo and compared with those for normal mice. AM depletion resulted in increased primary CTL responses and changed the kinetics of the CTL response. Flow cytometric analysis of lung and MLN cells showed that the percentage of CD8+ cells was not altered after AM depletion and that lung cells from AM-depleted mice had an increased capacity to lyse virus-infected cells. Upon restimulation in vitro, virus-specific CTL activity in lung cells of normal mice was similar to that in lung cells of AM-depleted mice. Furthermore, elimination of AM resulted in increased virus titers in the lung, but virus clearance as a function of time was not affected. Our results show that AM regulate virus-specific CTL responses during respiratory influenza virus infection by removing viral particles, by downregulating the priming and activity of CTL in MLN cells, and by inhibiting the expansion of virus-specific CTL in the lung.
病毒特异性细胞毒性T淋巴细胞（CTL）被认为通过直接溶解病毒感染的上皮细胞来清除呼吸道流感病毒感染。在本研究中，我们提供了肺泡巨噬细胞（AM）在调节肺部病毒特异性CTL反应中发挥作用的证据。在用脂质体介导的耗竭技术在体内选择性清除AM后再感染流感病毒，然后对肺和纵隔淋巴结（MLN）细胞的病毒特异性CTL活性进行体外检测，并与正常小鼠的进行比较。AM耗竭导致原发性CTL反应增强，并改变了CTL反应的动力学。对肺和MLN细胞的流式细胞术分析表明，AM耗竭后CD8 +细胞的百分比没有改变，并且来自AM耗竭小鼠的肺细胞裂解病毒感染细胞的能力增强。在体外再次刺激后，正常小鼠肺细胞中的病毒特异性CTL活性与AM耗竭小鼠肺细胞中的相似。此外，AM的清除导致肺中病毒滴度增加，但病毒清除随时间的变化不受影响。我们的结果表明，AM在呼吸道流感病毒感染期间通过去除病毒颗粒、下调MLN细胞中CTL的启动和活性以及抑制肺中病毒特异性CTL的扩增来调节病毒特异性CTL反应。
