Role of T cell receptor Vβ genes in Theiler's virus-induced demyelination of mice

M. Rodriguez, A. K. Patick, Larry R Pease, C. S. David

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Abstract

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 Vβ 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 Vβ-chain (Vβ5.2, Vβ8.3, Vβ5.1, Vβ8.2, Vβ5.3, Vβ8.1, Vβ13, Vβ12, Vβ11, Vβ9, Vβ6, Vβ15, Vβ17) compared with B10.RIII mice which are of identical MHC haplotype (H-2r) but have normal complement of Vβ TCR genes. In contrast, infection of C57L (H-2b) or C57BR (H-2k) mice which have deletion of the Vβ TCR genes (Vβ5.2, Vβ8.3, Vβ5.1, Vβ8.2, Vβ5.3, Vβ8.1, Vβ13, Vβ12, Vβ11, and Vβ9) resulted in few demyelinating lesions. Genetic segregation analysis of (B10.RIII × RIII S/J) × RIII S/J backcrossed mice and (B10.RIII × RIII S/J) F2 mice demonstrated correlation of increased susceptibility to demyelination with deletion of TCR Vβ 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 β-complex can influence susceptibility to virus-induced demyelination.

Original languageEnglish (US)
Pages (from-to)921-927
Number of pages7
JournalJournal of Immunology
Volume148
Issue number3
StatePublished - Feb 1 1992

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Theilovirus
T-Cell Receptor Genes
Demyelinating Diseases
Spinal Cord
Genes
Viruses
Infection
Haplotypes
Multiple Sclerosis

ASJC Scopus subject areas

  • Immunology

Cite this

Role of T cell receptor Vβ genes in Theiler's virus-induced demyelination of mice. / Rodriguez, M.; Patick, A. K.; Pease, Larry R; David, C. S.

In: Journal of Immunology, Vol. 148, No. 3, 01.02.1992, p. 921-927.

Research output: Contribution to journalArticle

Rodriguez, M, Patick, AK, Pease, LR & David, CS 1992, 'Role of T cell receptor Vβ genes in Theiler's virus-induced demyelination of mice', Journal of Immunology, vol. 148, no. 3, pp. 921-927.
Rodriguez, M. ; Patick, A. K. ; Pease, Larry R ; David, C. S. / Role of T cell receptor Vβ genes in Theiler's virus-induced demyelination of mice. In: Journal of Immunology. 1992 ; Vol. 148, No. 3. pp. 921-927.
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abstract = "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 Vβ 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 Vβ-chain (Vβ5.2, Vβ8.3, Vβ5.1, Vβ8.2, Vβ5.3, Vβ8.1, Vβ13, Vβ12, Vβ11, Vβ9, Vβ6, Vβ15, Vβ17) compared with B10.RIII mice which are of identical MHC haplotype (H-2r) but have normal complement of Vβ TCR genes. In contrast, infection of C57L (H-2b) or C57BR (H-2k) mice which have deletion of the Vβ TCR genes (Vβ5.2, Vβ8.3, Vβ5.1, Vβ8.2, Vβ5.3, Vβ8.1, Vβ13, Vβ12, Vβ11, and Vβ9) resulted in few demyelinating lesions. Genetic segregation analysis of (B10.RIII × RIII S/J) × RIII S/J backcrossed mice and (B10.RIII × RIII S/J) F2 mice demonstrated correlation of increased susceptibility to demyelination with deletion of TCR Vβ 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 β-complex can influence susceptibility to virus-induced demyelination.",
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