Induction of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in genetically resistant...

Theiler's murine encephalomyelitis virus-induced demyelinating disease, a murine model for multiple sclerosis, is the result of persistent infection which leads to a T cell-mediated immunopathology. Susceptible strains develop virus-specific DTH responses while resistant strains do not, and this response has been proposed as the basis for inflammation and demyelination. (C57BL/6 x DBA/2)F1 hybrid animals, normally resistant to TMEV-induced demyelinating disease, become susceptible when treated in vivo prior to infection with low dose cyclophosphamide. Comparable pretreatment of other resistant animals, C57BL/6 and CB6 (BALB/c x C57BL/6) F1 hybrids, does not render them susceptible (despite the H-2 identity of CB6F1 and B6D2F1 hybrids). Thus the "latent" susceptibility in B6D2F1 hybrids must be attributed to non-H-2 genes from the susceptible D2 parent. Resistance can be restored to CY-treated B6D2F1 animals by the adoptive transfer of splenic cells (including T cell enriched populations) from non-CY-treated donors. Resistance to TMEV-IDD in these animals, therefore, may involve active inhibition of a "latent" disease susceptibility.