Role of IFN-gamma responsiveness in CD8 T-cell-mediated viral clearance and demyelination in coronavirus-infected mice.

Immunocompetent, but not RAG1(-/-) mice infected with MHV-JHM develop demyelination. Transferred CD8 T cell-enriched splenocytes reconstitute demyelination, and this ability is dependent on donor IFN-gamma. We used IFN-gammaR1(-/-) mice to examine the target of IFN-gamma in CD8 T cell-mediated demyelination. In IFN-gammaR1(-/-)RAG1(-/-) recipients, demyelination is decreased, but not eliminated, while viral titers are significantly increased when compared to IFN-gammaR1(+/+)RAG1(-/-) recipients. IFN-gammaR1(-/-) CD8 T cells retain virus-specific effector function regardless of IFN-gammaR1 expression. Although IFN-gammaR1 responsiveness is critical for maximal demyelination, increased levels of infectious virus coupled with adoptive transfer of CD8 T cells may result in myelin destruction independent of IFN-gammaR1 expression.