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¹ Immune Regulation Lab – DI3 and ² Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

CORRESPONDENCE Matthias G. von Herrath: matthias{at}liai.org

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

M. Ejrnaes, C.M. Filippi, and M.M. Martinic contributed equally to this paper.

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