INDUCTION OF DEGENERATIVE BRAIN-LESIONS AFTER ADOPTIVE TRANSFER OF BRAIN LYMPHOCYTES FROM BORNA-DISEASE VIRUS-INFECTED RATS - PRESENCE OF CD8(-CELLS AND PERFORIN MESSENGER-RNA() T)

Lymphocytes were isolated from the brains of Borna disease virus-infec ted donor Lewis rats at various time points after infection. Cell popu lations were characterized by cytofluorometry, with special emphasis o n CD4(+) and CD8(+) cells. Testing of isolated lymphocytes revealed ma jor histocompatibility complex class I-restricted cytotoxic activity. Reverse transcription-PCR analyses of brain homogenates of infected do nors revealed the presence of CD8 mRNA after day 11 of infection and o f perforin mRNA between days 13 and 25 after infection. Adoptive trans fers of lymphocytes isolated from the brain at days 13 and 21 resulted in severe neurological symptoms, resembling experimental Borna diseas e. The onset of disease was dependent on the cell numbers transferred and was clearly related to the appearance of T cells in the brain. CD8 (+) T cells were found in the parenchyma, whereas CD4(+) T cells were found predominantly in perivascular locations. A disseminated lymphocy tic infiltration in the parenchyma was accompanied by severe morpholog ical alterations, including significant necrosis of neurons. Furthermo re, a prominent spongiform-like degeneration was observed; this increa sed over time and finally resulted in severe cortical brain atrophy. L ymphocytes obtained during the beginning chronic phase of experimental Borna disease in rats had no significant cytolytic capacity in vitro and were also not able to induce neurological symptoms typical of Born a disease after adoptive transfer. The data presented here show for th e first time that lymphocytes isolated from the site of the inflammato ry lesions, namely, the brains of diseased rats, induce the immunopath ological reaction and cause Borna disease. After transfer, the patholo gical alterations induced in the recipients exactly reflect those obse rved during experimentally induced Borna disease in rats, including ne crosis of neurons and glial cells and gross degeneration resulting in cortical brain atrophy. Evidence that the immunopathology of Borna dis ease is closely related to the presence of CD8(+) T cells in the brain parenchyma is provided.