Virus-Specific CD4 + T Cells Eliminate Borna Disease Virus from the Brain via Induction of Cytotoxic CD8 + T Cells

Abstract

Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4 + T-cell line prior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammatory reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus was cleared from the central nervous system. The loss of infectivity from the brain was confirmed by negative results by reverse transcription-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology. Most importantly, in vitro assays revealed that the T-cell line used for transfusion had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the appearance of CD8 + T cells and the expression of perforin in the brain. Testing of lymphocytes isolated from the brains of CD4 + T-cell-treated rats after challenge revealed high cytotoxic activity due to the presence of CD8 + cytotoxic T cells at time points when brain lymphocytes from 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.