Induction of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in genetically resistant mice.
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.
Olsberg
C
C
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611.
Pelka
A
A
Miller
S
S
Waltenbaugh
C
C
Creighton
T M
TM
Dal Canto
M C
MC
Lipton
H
H
Melvold
R
R
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004769:Enterovirus Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006824:Hybridization, Genetic; D006968:Hypersensitivity, Delayed / Q000235:genetics; D016219:Immunotherapy, Adoptive; D004680:Maus Elberfeld virus / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009103:Multiple Sclerosis / Q000209:etiology; D013045:Species Specificity
D003520:Cyclophosphamide