Abstract
Mice infected with the neurotropic coronavirus mouse hepatitis virus (MHV), attenuated strain J2.2 develop acute and chronic demyelinating disease with histopathological similarities to multiple sclerosis (MS). The process of demyelination is immune-mediated, as RAG1-/- or RAG2-/- (mice deficient in recombination activation enzyme), which lack B and T lymphocytes, do not develop demyelination upon infection with J2.2; however, if RAG1-/- mice are reconstituted with either MHV-immune CD4 or CD8 T cells, demyelination proceeded as in the immunocompetent mouse. While the pathogenic role of virus-specific CD4 and CD8 T cells and bystander CD8 T cells in this model has been demonstrated, less is known about the immune mechanisms that are controlling this anti-viral immune response. The cytokine IL-10 has been shown to be able to suppress an excessive immune response and protect the host against immune-mediated damage in EAE, an autoimmune model of multiple sclerosis. We investigated the role of IL-10 in demyelination using IL-10-/- mice. Additionally, we characterized the time, location, and antigen-specificity of IL-10 producing cells using IL-10gfp mice. Here, we demonstrate that IL-10 has a protective role in an animal model of MS and that the majority of IL-10 producing cells are MHV-specific T-cells located at the site of infection.
Funded in part by grants from the NIH and National Multiple Sclerosis Society.
