VIRUS-SPECIFIC CD4(-CELLS ELIMINATE BORNA-DISEASE VIRUS FROM THE BRAIN VIA INDUCTION OF CYTOTOXIC CD8(+) T-CELLS() T)

Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4(+) T cell line p rior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammato ry reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus w as cleared from the central nervous system. The loss of infectivity fr om the brain was confirmed by negative results by reverse transcriptio n-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology, Most importantly, in vitro assays r evealed that the T-cell line used for transfusion had no cytotoxic cap acity. The kinetics of virus clearance were paralleled by the appearan ce of CD8(+) T cells and the expression of perforin in the brain. Test ing of lymphocytes isolated from the brains of CD4(+) T-cell-treated r ats after challenge revealed high cytotoxic activity due to the presen ce of CD8(+) cytotoxic T cells at time points when brain lymphocytes f rom infected control rats induced low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma interferon were shown not to be involved in the elimination of virus from the brain.