Brooks, D.G. et al. Interleukin-10 determines viral clearance or persistence in vivo. Nat. Med. 12, 1301-1309

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: 27.36). 12/2006; 12(11):1301-9. DOI: 10.1038/nm1492
Source: PubMed


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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    • "Chronic infection of lymphocytic choriomeningitis virus (LCMV) in mice leads to increased IL-10 production, especially by dendritic cells, resulting in continued PD-1 expression on T cells [39] [41]. IL-10 signalling blockade by administration of anti-IL10R antibodies intraperitoneally facilitates eradication of chronic LCMV infection [39] [41]. Similarly, IL- 10R blockade prevents mouse cytomegalovirus (MCMV) persistence [2]. "
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    • "It is likely that the activation state of CD16+ monocytes accounts for this lower production of an immunoregulatory cytokine such as IL-10. The blockade of PD-1/PD-L1 interactions restores the immune response during HIV infection [17], [37]. Several evidence support that IL-10 and PD-1 constitute an amplification loop leading to immune impairment. "
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