Cutting Edge: CD8 T Cell-Mediated Demyelination Is IFN-γ Dependent in Mice Infected with a Neurotropic Coronavirus

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Abstract
Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. We showed previously that adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected RAG1−/− recipients (mice deficient in recombination activation gene 1) resulted in demyelination. Herein we show that transfer of CD8 T cell-enriched splenocytes from MHV-immune IFN-γ−/− donors resulted in a substantial decrease in demyelination (4.8% of the white matter of the spinal cord compared with 26.3% in those receiving cells from C57BL/6 donors). Similar numbers of lymphocytes were present in the CNS of recipients of either C57BL/6 or IFN-γ−/− CD8 T cells, suggesting that IFN-γ was not crucial for lymphocyte entry into the CNS. Rather, IFN-γ was critical for optimal activation or migration of macrophages or microglia into the white matter in the context of CD8 T cell-mediated demyelination.