Abstract
Semliki Forest Virus (SFV) encephalomyelitis has been used to study the pathogenesis of virus-induced demyelination and serves as a model for multiple sclerosis. SFV-infection of mice invariably leads to clinical weakness accompanied by CNS inflammation, viral clearance and primary demyelination by day 21 postinfection (pi), followed by recovery and remyelination by day 35 pi. We have applied this model to the examination of the effects of γδ T cells in antibody production and the pathogenesis of demyelinating lesions. SFV-infection of γδ T cell KO mice resulted in more severe clinical signs than in wild type (WT) B6 mice. SFV-infected WT and γδ KO mice both cleared virus by day 10 pi and inflammation was comparable. Demyelination also appeared to be similar in both groups except that KO mice did not exhibit extensive remyelination which was seen in WT mice by day 21. SFV-infected WT mice showed widespread remyelination by day 35 pi, whereas KO mice still displayed some demyelination through day 42 pi. Both WT and KO mice developed serum antibodies to SFV. However, the reactivity of WT sera with the SFV epitope, E2 T(h) peptide₂, was significantly higher than in KO sera. Immunization with E2 T(h) peptide₂ resulted in elevated antibody production to this peptide (p<0.05) and earlier remyelination (day 28 pi) in KO mice. Thus, our study has shown for the first time that immunization of SFV-infected γδ T cell KO mice with a viral peptide, E2 T(h) peptide₂ led to enhanced recovery and repair of the CNS.