Virus-induced demyelination in nude mice is mediated by γδ T cells

Infection of mice with mouse hepatitis virus (MHV), strain JHM, results in acute and chronic demyelination with many similarities to the human disease multiple sclerosis. This pathological process is primarily T cell-mediated and MHV infection of mice lacking B and T cells does not result in demyelination. In apparent contradiction to these results, robust demyelination is detected in MHV-infected young nude (athymic) mice. Herein, we show that demyelination in nude mice was mediated by gammadelta T cells. These cells, but not conventional CD4 or CD8 alphabeta T cells, were detected in the central nervous system of MHV-infected nude mice and their depletion with neutralizing antibody resulted in an 80% reduction in demyelination. These results show, for the first time, that gammadelta T cells can substitute for alphabeta T cells in a virus model of demyelination and further support a pathological role for gammadelta T cells in patients with multiple sclerosis.