Clonal expansion of infiltrating T cells in the spinal cords of SJL/J miceinfected with Theiler's virus

Intracerebral infection of susceptible mice with Theiler's murine encephalo myelitis virus results in immune-mediated inflammatory demyelination in the white matter and consequent clinical symptoms. This system has been utiliz ed as an important virus model for human multiple sclerosis, Although the p otential involvement of virus-specific: Th cells has been studied extensive ly, very little is known about the nature of T cells infiltrating the CNS d uring viral infection and their role in the development of demyelinating di sease, In this study, the clonal nature of T cells in the spinal cord durin g the disease course was analyzed using size spectratyping and sequencing o f the TCR beta-chain CDR3 region. These studies clearly indicate that T cel ls are clonally expanded in the CNS after viral infection, although the ove rall TCR repertoire appears to be diverse. The clonal expansion appears to be Ag-driven in that it includes Th cells specific for known viral epitopes , Interestingly, such restricted accumulation of T cells was not detectable in the infiltrates of mice with proteolipid protein peptide-induced experi mental autoimmune encephalomyelitis. The initial T cell repertoire (7-9 day s postinfection) seems to be more diverse than that observed in the later s tage (65 days) of virally induced demyelination, despite the more restricte d utilization of V beta subfamilies. These results strongly suggest continu ous stimulation and clonal expansion of virus-specific T cells in the CNS o f Theiler's murine encephalomyelitis virus-infected mice during the entire course of demyelinating disease.