Resolution of a chronic viral infection after interleukin-10 receptor blockade
M Ejrnaes, CM Filippi, MM Martinic, EM Ling… - The Journal of …, 2006 - rupress.org
M Ejrnaes, CM Filippi, MM Martinic, EM Ling, LM Togher, S Crotty, MG von Herrath
The Journal of experimental medicine, 2006•rupress.orgA 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 …
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 …
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.
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