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

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.
AuthorsMette Ejrnaes, Christophe M Filippi, Marianne M Martinic, Eleanor M Ling, Lisa M Togher, Shane Crotty, Matthias G von Herrath
JournalThe Journal of experimental medicine (J Exp Med) Vol. 203 Issue 11 Pg. 2461-72 (Oct 30 2006) ISSN: 0022-1007 [Print] United States
PMID17030951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Monoclonal
  • Immune Sera
  • Receptors, Interleukin-10
  • Interleukin-10
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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