Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Clement, Mathew, Marsden, Morgan, Stacey, Maria, Abdul-Karim, Juneid, Gimeno Brias, Silvia, Costa Bento, Diana Filipa, Scurr, Martin, Weaver, Casey, Carlesso, Gianluca, Clare, Simon, Jones, Simon, Godkin, Andrew, Ghazal, Peter, Jones, Gareth W. and Humphreys, Ian 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

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

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
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: 26 Dec 2018 21:50
URI: http://orca.cf.ac.uk/id/eprint/96399

Citation Data

Cited 17 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics