Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands

Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337, De Trez, Carl, Kinkade, April, Benedict, Chris A., Croft, Michael and Ware, Carl F. 2007. Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. Journal of Experimental Medicine 204 (5) , pp. 1217-25. 10.1084/jem.20062424

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Abstract

The salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. Despite control of viral infection by strong T cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. Here, we show that T cell immunity in the salivary glands is limited by the induction of CD4 T cells expressing the regulatory cytokine interleukin (IL)-10. Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced viral load in the salivary glands, but not in the spleen. The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumulation of CD4 T cells expressing interferon [gamma], suggesting that IL-10R signaling limits effector T cell differentiation. Consistent with this, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced effector T cell differentiation and increased the number of interferon [gamma]–producing T cells, thus limiting virus replication in the salivary glands. Collectively, the results indicate that modulating effector T cell differentiation can counteract pathogen exploitation of the mucosa, thus limiting persistent virus replication and transmission.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Publisher’s copyright requirements: “Ownership of copyright in the Work remains with the authors. The Authors retain the non-exclusive right to do anything they want with the Work, so long as the Authors provide attribution to the place of original publication. The retained right specifically includes the right to post the Work on the authors’ or their institutions’ web sites.” See: http://www.rupress.org/site/subscriptions/terms.xhtml
Publisher:	Rockefeller University Press
ISSN:	15409538
Last Modified:	12 May 2023 22:57
URI:	https://orca.cardiff.ac.uk/id/eprint/349

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