Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence.

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Clement M,Marsden M,Stacey MA,Abdul-Karim J,Gimeno Brias S,Costa Bento D,Scurr MJ,Ghazal P,Weaver CT,Carlesso G,Clare S,Jones SA,Godkin A,Jones GW,Humphreys IR

doi

10.1371/journal.ppat.1006050

subject

Has Abstract

pub_date

2016-12-07 00:00:00

pages

e1006050

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-01245

journal_volume

12

pub_type

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