Interleukin-10 determines viral clearance or persistence in vivo

Viral Immunobiology Laboratory, Molecular and Integrative Neuroscience Department, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Medicine (Impact Factor: 28.05). 12/2006; 12(11):1301-9. DOI: 10.1038/nm1492
Source: PubMed

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.

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Available from: Dorian McGavern, Oct 28, 2014
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