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

Templeton, Steven P.; Perlman, Stanley

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-γ. We used IFN-γR1(−/−) mice to examine the target of IFN-γ in CD8 T cell-mediated demyelination. In IFN-γR1(−/−)RAG1(−/−) recipients, demyelination is decreased, but not eliminated, while viral titers are significantly increased when compared to IFN-γR1(+/+)RAG1(−/−) recipients. IFN-γR1(−/−) CD8 T cells retain virus-specific effector function regardless of IFN-γR1 expression. Although IFN-γR1 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-γR1 expression.