Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination

M. Rodriguez, C. Nickerson, A. K. Patick, C. S. David

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2(s,f,) or (v) mice but not H-2(b) mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2(f) or H-2(v) haplotype. In contrast, H-2(s) (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2(s) (HLA-B27-) littermate mice. In addition, none of the eight H-2(s) mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2(b)) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse.

Original languageEnglish (US)
Pages (from-to)2596-2602
Number of pages7
JournalJournal of Immunology
Volume146
Issue number8
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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