Human class I major histocompatibility complex transgene prevents virus‐induced demyelination in susceptible mutant B 10.d2 dml mice

• Published in: Annals of Neurology
• Main Authors: Rodriguez, M., Pedrinaci, S., David, C. S.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 1993
• Subjects: DML
• Online Access: http://dx.doi.org/10.1002/ana.410330211; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fana.410330211; https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.410330211

Abstract Theiler's murine encephalomyelitis virus (TMEV) induces immune‐mediated demyelination in susceptible strains of mice, providing an excellent model for multiple sclerosis. Class I genes within the major histocompatibility complex locus (H‐2D region)play a major role in determining whether strains of mice develop chronic in determining whether strains of mice develop chronic demyelination and TMEV persistence. B 10.D2 dml mice with deletion in the 3′ end of D d and the 5′ end of L d genes develop the most prominent demyelination in comparison with resistant B10. D2 mice normal complementation of H‐2D region genes. We tested whether expression of a class I human transgene (HLA‐B27) would modulate virus‐induced demyelination in mutant B10.D2 dml mice. Transgenic B10.D2 dml (HLA‐B27 + ) mice infected with virus showed dramatic decrease in the extent of demyelination ( p < 0.0001) and virus antigen expression in spinal cord compared with littermate controls without the human class I transgene. These experiments demonstrate that transgenic expression of a human class I major histocompatibility complex locus molecule can prevent demyelination induced by a virus in mutant mice.