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: | 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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