Role of T cell receptor V beta genes in Theiler's virus-induced demyelination of mice.
Intracerebral infection of certain strains of mice with Theiler's virus results in chronic immune-mediated demyelination in spinal cord. We used mouse mutants with deletion of the V beta class of TCR genes to examine the role of TCR genes in this demyelinating disease which is similar to multiple sclerosis. Quantitative analysis of spinal cord lesions demonstrated a markedly increased number and extent of demyelinated lesions in persistently infected RIII S/J mice which have a massive deletion of the TCR V beta-chain (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, V beta 9, V beta 6, V beta 15, V beta 17) compared with B10.RIII mice which are of identical MHC haplotype (H-2r) but have normal complement of V beta TCR genes. In contrast, infection of C57L (H-2b) or C57BR (H-2k) mice which have deletion of the V beta TCR genes (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, and V beta 9) resulted in few demyelinating lesions. Genetic segregation analysis of (B10.RIII x RIII S/J) x RIII S/J backcrossed mice and (B10.RIII x RIII S/J) F2 mice demonstrated correlation of increased susceptibility to demyelination with deletion of TCR V beta genes. The increase in number of demyelinating lesions correlated with increase in number of virus-Ag+ cells in spinal cord. These experiments provide strong evidence that the structural diversity at the TCR beta-complex can influence susceptibility to virus-induced demyelination.
Rodriguez
M
M
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Patick
A K
AK
Pease
L R
LR
David
C S
CS
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002872:Chromosome Deletion; D003711:Demyelinating Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004769:Enterovirus Infections / Q000276:immunology* / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D004680:Maus Elberfeld virus / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta