Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 10, Pages 6768-6776Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.10.6768
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Funding
- Medical Research Council [G9818340, G0401620, G116/131] Funding Source: researchfish
- MRC [G116/131, G0401620, G9818340] Funding Source: UKRI
- Medical Research Council [G0401620, G116/131, G9818340] Funding Source: Medline
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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 breakdown in immunocompromised patients.
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