Interleukin-10 determines viral clearance or persistence in vivo.

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.

• Authors: David G Brooks, Matthew J Trifilo, Kurt H Edelmann, Luc Teyton, Dorian B McGavern, Michael B A Oldstone
• Journal: Nature medicine (Nat Med) Vol. 12 Issue 11 Pg. 1301-9 (Nov 2006) ISSN: 1078-8956 [Print] United States
• PMID: 17041596 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-10
• Interleukin-10

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Flow Cytometry
• HIV (physiology)
• Hepacivirus (physiology)
• Immunologic Memory
• Interleukin-10 (physiology)
• Lymphocytic choriomeningitis virus (physiology)
• Mice
• Receptors, Interleukin-10 (antagonists & inhibitors)
• Reverse Transcriptase Polymerase Chain Reaction