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The Journal of Immunology, Vol 151, Issue 1 266-276, Copyright © 1993 by American Association of Immunologists
ARTICLES |
M Rodriguez, AJ Dunkel, RL Thiemann, J Leibowitz, M Zijlstra and R Jaenisch
Department of Neurology, Mayo Clinic, Rochester, MN 55901.
Intracerebral infection of susceptible strains of mice with Theiler's virus, a picornavirus, results in central nervous system demyelination, which is similar to multiple sclerosis. Immunogenetic experiments indicate that the MHC (H-2) and, in particular, the D region that controls class I-restricted immune responses, is an important determinant to development of demyelination. We tested whether disruption of beta 2-microglobulin (beta 2-m) would abrogate resistance to demyelinating disease normally observed in H-2b mice. All (C57BI/6 x 129)F3 mice transgenic for homozygous beta 2-m gene disruption (-/-) developed chronic demyelination after Theiler's murine encephalomyelitis virus infection, whereas none of the infected littermates with normal expression of class I MHC (beta 2-m, +/+) developed demyelination. Demyelinated lesions showed class II MHC expression, macrophages, and TNF but no class I MHC expression or CD8+ T cells. No correlation was observed between development of demyelination and delayed-type hypersensitivity responses to virus Ag. Despite the presence of demyelinating lesions, none of the infected beta 2-m (-/-) mice developed neurologic deficits. Infectious virus and virus Ag persisted in the central nervous systems of infected beta 2-m (-/-) mice but not in beta 2-m (+/+) mice. These experiments support the hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus- induced demyelination. Development of chronic neurologic deficits as observed in immunocompetent susceptible strains of mice may be dependent on the presence of class I MHC and CD8+ T cells.
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A. J. Johnson, M. K. Njenga, M. J. Hansen, S. T. Kuhns, L. Chen, M. Rodriguez, and L. R. Pease Prevalent Class I-Restricted T-Cell Response to the Theiler's Virus Epitope Db:VP2121-130 in the Absence of Endogenous CD4 Help, Tumor Necrosis Factor Alpha, Gamma Interferon, Perforin, or Costimulation through CD28 J. Virol., May 1, 1999; 73(5): 3702 - 3708. [Abstract] [Full Text]
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