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J Exp Med. 2006 Oct 30;203(11):2461-72. Epub 2006 Oct 9.

Resolution of a chronic viral infection after interleukin-10 receptor blockade.

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  • 1Immune Regulation Lab - DI3, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Abstract

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon gamma production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8alpha+ dendritic cell (DC) numbers declined early after infection, whereas CD8alpha- DC numbers were not affected. CD8alpha- DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10 priming by CD8alpha- DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

PMID:
17030951
[PubMed - indexed for MEDLINE]
PMCID:
PMC2118120
Free PMC Article
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