Interleukin-10 determines viral clearance or persistence in vivo

DG Brooks, MJ Trifilo, KH Edelmann, L Teyton… - Nature medicine, 2006 - nature.com
DG Brooks, MJ Trifilo, KH Edelmann, L Teyton, DB McGavern, MBA Oldstone
Nature medicine, 2006nature.com
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 …
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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