We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cytomegalovirus-Specific IL-10-Producing CD4<sup>+</sup> T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence.
- Authors
Clement, Mathew; Marsden, Morgan; Stacey, Maria A.; Abdul-Karim, Juneid; Gimeno Brias, Silvia; Costa Bento, Diana; Scurr, Martin J.; Ghazal, Peter; Weaver, Casey T.; Carlesso, Gianluca; Clare, Simon; Jones, Simon A.; Godkin, Andrew; Jones, Gareth W.; Humphreys, Ian R.
- 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.
- Subjects
CYTOMEGALOVIRUSES; HERPESVIRUS diseases; LABORATORY mice; INTERLEUKINS; CHEMOKINES; TRANSCRIPTION factors
- Publication
PLoS Pathogens, 2016, Vol 12, Issue 12, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1006050