Precursors of Borna disease virus-specific T cells in secondary lymphatic tissue of experimentally infected rats.

Borna disease in rats represents an experimental model to study the immunopathological role of T cells in central nervous system disease. Adoptive transfer experiments were performed to investigate homing properties of T cells that infiltrate the brains of infected animals. Lymphocytes isolated from the brains of diseased rats were labelled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and transferred into immunosuppressed infected recipients. In recipient rats displaying neurological disease, labeled lymphocytes were demonstrated in the vicinity of brain cell lesions, suggesting that the neuronal destruction was dependent on the presence of transferred lymphocytes. Furthermore, the presence of virus-specific cytotoxic T cells was scrutinized in secondary lymphatic tissue and the functional activity of lymphocytes isolated from spleens, cervical lymph nodes, and mesenteric lymph nodes of infected animals was tested immediately after isolation and after in vitro restimulation. The data presented here indicate that precursors of Borna disease virus (BDV)-specific CD8(+) T cells are present and cytotoxic activity was demonstrated after in vitro cocultivation with infected cells in cervical lymph nodes and spleens but not in mesenteric lymphoid tissue. Adoptive transfer of in vitro restimulated T cells induced alterations in BDV-infected, immunosuppressed rats that resemble the well-defined clinical symptoms and neuropathology of Borna disease. This report provides for the first time formal evidence that virus-specific cytotoxic T cells are primed in the periphery after BDV infection, a disease that exclusively manifests itself in the central nervous system.