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Nat Med. 2006 Nov;12(11):1301-9. Epub 2006 Oct 15.

Interleukin-10 determines viral clearance or persistence in vivo.

Author information

1
Viral Immunobiology Laboratory, Molecular and Integrative Neuroscience Department, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. dbrooks@scripps.edu

Abstract

Persistent viral infections are a major health concern. One obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral T cells. Although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of T-cell activity and promote viral persistence are unknown. Herein we document that persistent viral infection in mice results in a significant upregulation of interleukin (IL)-10 by antigen-presenting cells, leading to impaired T-cell responses. Genetic removal of Il10 resulted in the maintenance of robust effector T-cell responses, the rapid elimination of virus and the development of antiviral memory T-cell responses. Therapeutic administration of an antibody that blocks the IL-10 receptor restored T-cell function and eliminated viral infection. Thus, we identify a single molecule that directly induces immunosuppression leading to viral persistence and demonstrate that a therapy to neutralize IL-10 results in T-cell recovery and the prevention of viral persistence.

PMID:
17041596
PMCID:
PMC2535582
DOI:
10.1038/nm1492
[Indexed for MEDLINE]
Free PMC Article

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