1. Reversal of chronic to resolved infection by IL-10 blockade is LCMV strain dependent.
- Author
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Richter K, Perriard G, and Oxenius A
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Chronic Disease, Dendritic Cells immunology, Dendritic Cells virology, Interleukin-10 genetics, Interleukin-10 immunology, Lymphocytic Choriomeningitis genetics, Lymphocytic Choriomeningitis virology, Lymphocytic choriomeningitis virus physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Interleukin-10 antagonists & inhibitors, Virus Replication, Interleukin-10 antagonists & inhibitors, Lymphocytic Choriomeningitis immunology, Lymphocytic choriomeningitis virus immunology
- Abstract
Chronic viral infections lead to CD8(+) T-cell exhaustion, characterized by impaired cytokine secretion. The immune-regulatory cytokine IL-10 promotes chronicity of infection with lymphocytic choriomeningitis virus (LCMV) Clone 13, as absence of IL-10 or blocking of IL-10R during early LCMV Clone 13 infection results in viral clearance. Thus, treatment of humans suffering from chronic viral infections with IL-10 neutralizing or IL-10R blocking antibodies was proposed to boost virus-specific T-cell responses to enhance control or even clear the viral infection. Here we demonstrate that although CD4(+) and CD8(+) T cells can produce elevated levels of cytokines in IL-10(-/-) mice early after infection compared with WT mice, IL-10(-/-) mice cannot clear an infection with the quicker replicating LCMV strain Docile, eventually resulting in T-cell exhaustion. These data suggest that the success of IL-10 blockade to control chronic viral infections may critically depend on the virulence of the infecting strain., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
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