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

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.