Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Genetic Engineering Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Immunol. 2019 May;20(5):602-612. doi: 10.1038/s41590-019-0342-0. Epub 2019 Mar 18.
Despite intense interest in antiviral T cell priming, the routes by which virions move in lymph nodes (LNs) are imperfectly understood. Current models fail to explain how virus-infected cells rapidly appear within the LN interior after viral infection. To better understand virion trafficking in the LN, we determined the locations of virions and infected cells after administration to mice of vaccinia virus or Zika virus. Notably, many rapidly infected cells in the LN interior were adjacent to LN conduits. Through the use of confocal and electron microscopy, we clearly visualized virions within conduits. Functionally, CD8 T cells rapidly and preferentially associated with vaccinia virus-infected cells in the LN paracortex, which led to T cell activation in the LN interior. These results reveal that it is possible for even large virions to flow through LN conduits and infect dendritic cells within the T cell zone to prime CD8 T cells.
尽管人们对抗病毒 T 细胞的启动非常感兴趣,但病毒粒子在淋巴结(LN)中的移动途径仍不完全清楚。目前的模型无法解释病毒感染后病毒感染细胞如何在 LN 内部迅速出现。为了更好地了解 LN 中的病毒粒子运输,我们在给小鼠接种牛痘病毒或寨卡病毒后,确定了病毒粒子和感染细胞的位置。值得注意的是,LN 内部许多快速感染的细胞都与 LN 导管相邻。通过使用共聚焦和电子显微镜,我们清楚地观察到了导管内的病毒粒子。功能上,CD8 T 细胞迅速且优先与 LN 皮质旁区的牛痘病毒感染细胞结合,这导致了 LN 内部 T 细胞的激活。这些结果表明,即使是大型病毒粒子也可以通过 LN 导管流动,并感染 T 细胞区的树突状细胞来激活 CD8 T 细胞。