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

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 pape...

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Veröffentlicht in:The Journal of experimental medicine Jg. 203; H. 11; S. 2461
Hauptverfasser: Ejrnaes, Mette, Filippi, Christophe M, Martinic, Marianne M, Ling, Eleanor M, Togher, Lisa M, Crotty, Shane, von Herrath, Matthias G
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 30.10.2006
Schlagworte:
Animals
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - therapeutic use
Chronic Disease
Immune Sera - administration & dosage
Interleukin-10 - antagonists & inhibitors
Interleukin-10 - deficiency
Interleukin-10 - genetics
Interleukin-10 - secretion
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - metabolism
Lymphocytic Choriomeningitis - therapy
Lymphocytic choriomeningitis virus - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Rats
Receptors, Interleukin-10 - antagonists & inhibitors
Receptors, Interleukin-10 - biosynthesis
Receptors, Interleukin-10 - immunology
ISSN:0022-1007
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-1007
DOI:10.1084/jem.20061462