| Summary: | <p>Abstract</p> <p>Background</p> <p>Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV<sub>ARM</sub>) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMV<sub>Clone13</sub>, which causes functional inactivation of effector T cells and viral persistence. The mechanism by which LCMV<sub>Clone13 </sub>suppresses the antiviral immune response and persists in its host is unknown.</p> <p>Results</p> <p>Here we demonstrate that infection with LCMV<sub>Clone13</sub>, but not with LCMV<sub>ARM</sub>, 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<sub>Clone13</sub>-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<sup>+ </sup>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 <it>in vitro </it>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.</p> <p>Conclusion</p> <p>Our data suggest that IL-10 plays an early role in LCMV<sub>Clone13</sub>-induced tolerance, although other factors collaborate with IL-10 to induce virus-specific tolerance.</p>
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