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- Title
Interleukin-10 determines viral clearance or persistence in vivo.
- Authors
Brooks, David G.; Trifilo, Matthew J.; Edelmann, Kurt H.; Teyton, Luc; McGavern, Dorian B.; Oldstone, Michael B. A.
- 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.
- Subjects
VIRUS diseases; INTERLEUKIN-10; ANTIVIRAL agents; T cells; ANTIGEN presenting cells; IMMUNOSUPPRESSION; LYMPHOCYTIC choriomeningitis
- Publication
Nature Medicine, 2006, Vol 12, Issue 11, p1301
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1492