Cytomegalovirus-specific IL-10-producing CD4+ T cells are governed by type-I IFN-induced IL-27 and promote virus persistence

Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Marsden, Morgan, Stacey, Maria, Abdul-Karim, Juneid, Gimeno Brias, Silvia, Costa Bento, Diana Filipa, Scurr, Martin ORCID: https://orcid.org/0000-0002-4120-0688, Weaver, Casey, Carlesso, Gianluca, Clare, Simon, Jones, Simon ORCID: https://orcid.org/0000-0001-7297-9711, Godkin, Andrew ORCID: https://orcid.org/0000-0002-1910-7567, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228, Jones, Gareth W. and Humphreys, Ian ORCID: https://orcid.org/0000-0002-9512-5337 2016. Cytomegalovirus-specific IL-10-producing CD4+ T cells are governed by type-I IFN-induced IL-27 and promote virus persistence. Plos Pathogens 12 (12) , e1006050. 10.1371/journal.ppat.1006050

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Abstract

CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology Q Science > QR Microbiology > QR355 Virology
Uncontrolled Keywords:	cytomegalovirus, CD4+ T-cells, IL-10, IL-27R, type-I IFN
Additional Information:	Copyright: © 2016 Clement et al. This is an open access article distributed under the terms of the Creative Commons Attribution License
Publisher:	Public Library of Science
ISSN:	1553-7366
Funders:	Wellcome Trust, MRC, Arthritis Research UK, BBSRC/ESPRC
Date of First Compliant Deposit:	14 March 2017
Date of Acceptance:	9 November 2016
Last Modified:	11 Oct 2023 19:33
URI:	https://orca.cardiff.ac.uk/id/eprint/96399

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