Theiler's virus infection of beta 2-microglobulin-deficient mice.
Theiler's virus, a murine picornavirus, persists in the central nervous systems of susceptible mice and induces a chronic demyelinating disease. Susceptibility or resistance to this disease is controlled in part by the H2-D locus of the major histocompatibility complex (MHC). For this reason, it has been proposed that CD8+ class I-restricted cytotoxic T cells play a main role in the pathogenesis of this viral infection. We recently reported the existence of anti-virus CD8+ cytotoxic T cells in the course of Theiler's virus infection. In the present study, we examined the role of these effector cells in mice in which the beta 2-microglobulin gene had been disrupted. These mice fail to express class I MHC molecules and therefore lack CD8+ T cells. The mice are derived from a C57BL/6 x 129/Ola cross and are H-2b, a haplotype associated with resistance to Theiler's virus infection. beta 2-Microglobulin-deficient mice (beta 2m-/-mice) failed to clear the virus, developed demyelination, and, interestingly, did not succumb to early infection. These results demonstrate that CD8+ T cells are required to clear Theiler's virus infection. In contrast with a current hypothesis, they also demonstrate that CD8+ T cells are not major mediators of the demyelinating disease.
Fiette
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L
Unité des Virus Lents, UA 1157 Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
Aubert
C
C
Brahic
M
M
Rossi
C P
CP
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D003433:Crosses, Genetic; D004769:Enterovirus Infections / Q000276:immunology*; D005805:Genes, MHC Class I; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000276:immunology; D004680:Maus Elberfeld virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000276:immunology*; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014774:Virulence; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000276:immunology
D016827:CD8 Antigens; D001613:beta 2-Microglobulin