Bekiaris Vasileios, Timoshenko Olga, Hou Tie Zheng, Toellner Kai, Shakib Saba, Gaspal Fabrina, McConnell Fiona M, Parnell Sonia M, Withers David, Buckley Chris D, Sweet Clive, Yokoyama Wayne M, Anderson Graham, Lane Peter J L
Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, UK.
J Immunol. 2008 May 15;180(10):6768-76. doi: 10.4049/jimmunol.180.10.6768.
In this study, we show that in the absence of a protective NK cell response, murine CMV causes destruction of splenic white and red pulp pulp areas in the first few days of infection. Destruction of T zone stroma is associated with almost complete loss of dendritic cells and T cells. We provide evidence that the virus replicates in red and white pulp stroma in vivo and in vitro. Control of white pulp viral replication is associated with migration of murine CMV-specific activated NK cells to white pulp areas, where they associate directly with podoplanin-expressing T zone stromal cells. Our data explain how NK cells protect the lymphoid-rich white pulp areas from CMV, allowing protective adaptive T cell-dependent immune responses to develop, and how this mechanism might break down in immunocompromised patients.
在本研究中，我们发现，在缺乏保护性NK细胞应答的情况下，小鼠巨细胞病毒在感染后的头几天会导致脾脏白髓和红髓区域遭到破坏。T细胞区基质的破坏与树突状细胞和T细胞几乎完全丧失有关。我们提供的证据表明，该病毒在体内和体外的红髓和白髓基质中复制。白髓病毒复制的控制与小鼠巨细胞病毒特异性活化NK细胞迁移至白髓区域有关，在该区域它们直接与表达血小板内皮细胞黏附分子-1的T细胞区基质细胞相关联。我们的数据解释了NK细胞如何保护富含淋巴细胞的白髓区域免受巨细胞病毒侵害，从而使保护性适应性T细胞依赖性免疫应答得以发展，以及这种机制在免疫功能低下患者中可能如何失效。
