Role of natural killer cells as immune effectors in encephalitis and demyelination induced by Theiler's virus.
Infection of susceptible mice (SJL) with Theiler's murine encephalitis virus (TMEV) causes a biphasic disease characterized by gray matter inflammation followed by late chronic demyelination. The role of NK cells was studied in this model by using susceptible (SJL) or resistant (C57BL/10) mice. CNS TMEV titer were higher in SJL compared with C57BL/10 mice, correlating with a 50% lower NK cell activity in the SJL than in the C57BL/10 mice. When resistant (C57BL/10) mice were depleted of NK cells using either mAb NK1.1 or polyclonal anti-asialo-GM1, TMEV induced the development of diffuse encephalitis and meningitis early in the postinfection period (days 6 to 11). However, the second phase of TMEV-induced CNS disease (demyelination) was observed only in resistant C57BL/10 mice treated with anti-asialo-GM1. Experiments with beige/beige mice of C57BL/10 background showed a mild degree of gray matter inflammation but no demyelination. In conclusion, NK cells are critical effectors in protecting against TMEV-induced gray matter disease, whereas a different population of either NK1.1- NK cells, or other activated lymphocytes may be critical in resistance/susceptibility to demyelination.
Paya
C V
CV
Division of Infectious Diseases, Mayo Medical School, Rochester, MN 55905.
Patick
A K
AK
Leibson
P J
PJ
Rodriguez
M
M
D000818:Animals; D003711:Demyelinating Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004770:Enterovirus / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D004680:Maus Elberfeld virus / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013045:Species Specificity; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D014779:Virus Replication