1. Resolution of a chronic viral infection after interleukin-10 receptor blockade.
- Author
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Ejrnaes M, Filippi CM, Martinic MM, Ling EM, Togher LM, Crotty S, and von Herrath MG
- Subjects
- Animals, Antibodies, Monoclonal administration & dosage, Chronic Disease, Immune Sera administration & dosage, Interleukin-10 antagonists & inhibitors, Interleukin-10 deficiency, Interleukin-10 genetics, Interleukin-10 metabolism, Lymphocytic Choriomeningitis metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Rats, Receptors, Interleukin-10 biosynthesis, Antibodies, Monoclonal therapeutic use, Lymphocytic Choriomeningitis immunology, Lymphocytic Choriomeningitis therapy, Lymphocytic choriomeningitis virus immunology, Receptors, Interleukin-10 antagonists & inhibitors, Receptors, Interleukin-10 immunology
- 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.
- Published
- 2006
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