Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection

Vasileios Bekiaris, Olga Timoshenko, Tie Zheng Hou, Kai Toellner, Saba Shakib, Fabrina Gaspal, Fiona M. McConnell, Sonia M. Parnell, David Withers, Chris D. Buckley, Clive Sweet, Wayne M. Yokoyama, Graham Anderson, Peter J.L. Lane

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35 Scopus citations

Abstract

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-spccific 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.

Original languageEnglish
Pages (from-to)6768-6776
Number of pages9
JournalJournal of Immunology
Volume180
Issue number10
DOIs
StatePublished - Jan 1 2008

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    Bekiaris, V., Timoshenko, O., Hou, T. Z., Toellner, K., Shakib, S., Gaspal, F., McConnell, F. M., Parnell, S. M., Withers, D., Buckley, C. D., Sweet, C., Yokoyama, W. M., Anderson, G., & Lane, P. J. L. (2008). Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection. Journal of Immunology, 180(10), 6768-6776. https://doi.org/10.4049/jimmunol.180.10.6768