Reversal of chronic to resolved infection by IL-10 blockade is LCMV strain dependent


Full correspondence: Dr. Kirsten Richter, Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI G407, 8093 Zurich, Switzerland

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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.