Axonal damage is T cell mediated and occurs concomitantly with demyelination in mice infected with a neurotropic coronavirus

Mice infected with mouse hepatitis virus (MHV) strain JHM develop primary d emyelination. Herein we show that axonal damage occurred in areas of demyel ination and also in adjacent areas devoid of myelin damage. Immunodeficient MHV-infected RAG1-/- mice (mice defective in recombinase activating gene 1 expression) do not develop demyelination unless they receive splenocytes f rom a mouse previously immunized against MHV (G. F. Wu, A. Dandekar, L. Pew e, and S. Perlman, J. Immunol, 165:2278-2286, 2000). In the present study, we show that adoptive transfer of T cells was also required for the majorit y of the axonal injury observed in these animals, Both demyelination and ax onal damage were apparent by 7 days posttransfer. Recent data suggest that axonal injury is a major factor in the long-term disability observed in pat ients with multiple sclerosis, Our data demonstrate that immune system-medi ated damage to axons is also a common feature in mice with MHV induced demy elination. Remarkably, there appeared to be a minimal, if any, interval of time between the appearance of demyelination and that of axonal injury.