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(American Journal of Pathology. 2002;161:1255-1263.)
© 2002 American Society for Investigative Pathology

Regular Articles

Virus-Induced Demyelination in Nude Mice Is Mediated by {gamma}{delta} T Cells

Ajai A. Dandekar* and Stanley Perlman*{dagger}{ddagger}

From the Interdisciplinary Program in Immunology* and the Departments of Pediatrics{dagger} and Microbiology,{ddagger} University of Iowa, Iowa City, Iowa

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 {gamma}{delta} T cells. These cells, but not conventional CD4 or CD8 {alpha}ß 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 {gamma}{delta} T cells can substitute for {alpha}ß T cells in a virus model of demyelination and further support a pathological role for {gamma}{delta} T cells in patients with multiple sclerosis.




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