Bystander CD8 T-Cell-Mediated Demyelination is Interferon-γ -Dependent in a Coronavirus Model of Multiple Sclerosis

Abstract

Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-γ (IFN-γ)-dependent. The absence of IFN-γ abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-γ contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process.