Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV_ARM) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMV_Clone13, which causes functional inactivation of effector T cells and viral persistence. The mechanism by which LCMV_Clone13 suppresses the antiviral immune response and persists in its host is unknown.

Here we demonstrate that infection with LCMV_Clone13, but not with LCMV_ARM, resulted in a steady increase in the serum levels of the immuno-inhibitory cytokine, IL-10. Blockade of IL-10 using neutralizing monoclonal antibody injections in LCMV_Clone13-infected mice led to dramatically enhanced effector T cell responses at 8 days post-infection. Even though IL-10 blockade resulted in decreased viral titers, the generation and maintenance of memory T cells was still compromised. The functional inactivation of CD8⁺ T cells in IL-10-blocked, chronically infected mice 30 days post-infection was incomplete as potent CTL (cytotoxic T lymphocytes) could be generated by in vitro re-stimulation. IL-10 knockout mice showed a similar pattern of antiviral CD8 T cell responses: early antiviral T cells were dramatically increased and viral levels were decreased; however, CD8 T cells in IL-10 knockout mice were also eventually anergized and these mice became persistently infected.

Our data suggest that IL-10 plays an early role in LCMV_Clone13-induced tolerance, although other factors collaborate with IL-10 to induce virus-specific tolerance.