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.
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Authors | Mette Ejrnaes, Christophe M Filippi, Marianne M Martinic, Eleanor M Ling, Lisa M Togher, Shane Crotty, Matthias G von Herrath |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 203
Issue 11
Pg. 2461-72
(Oct 30 2006)
ISSN: 0022-1007 [Print] United States |
PMID | 17030951
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Monoclonal
- Immune Sera
- Receptors, Interleukin-10
- Interleukin-10
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Topics |
- Animals
- Antibodies, Monoclonal
(administration & dosage, therapeutic use)
- Chronic Disease
- Immune Sera
(administration & dosage)
- Interleukin-10
(antagonists & inhibitors, deficiency, genetics, metabolism)
- Lymphocytic Choriomeningitis
(immunology, metabolism, therapy)
- Lymphocytic choriomeningitis virus
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Rats
- Receptors, Interleukin-10
(antagonists & inhibitors, biosynthesis, immunology)
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