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

Author:

Ejrnaes Mette1,Filippi Christophe M.1,Martinic Marianne M.1,Ling Eleanor M.1,Togher Lisa M.1,Crotty Shane2,von Herrath Matthias G.1

Affiliation:

1. Immune Regulation Lab – DI3

2. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

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 γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α− DC numbers were not affected. CD8α− 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 CD8α− DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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