Ly49H super(+) NK Cells Migrate to and Protect Splenic White Pulp Stroma from Murine Cytomegalovirus Infection

• Published in: The Journal of immunology (1950) 2008-05, Vol.180 (10), p.6768-6776
• Main Authors: 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 JL
• Format: Article
• Language: English
• Subjects: Cytomegalovirus; Murine cytomegalovirus
• ISSN: 0022-1767; 1550-6606

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.