CD8(+) T lymphocytes mediate Borna disease virus-induced immunopathology independently of perforin

Perforin-mediated lysis of target cells is the major antiviral effector mec hanism of CD8(+) T lymphocytes. We have analyzed the role of perforin in a mouse model for CD8(+) T-cell-mediated central nervous system (CNS) immunop athology induced by Borna disease virus. When a defective perforin gene was introduced into the genetic background of the Borna disease-susceptible mo use strain MRL, the resulting perforin-deficient mice developed strong neur ological disease in response to infection indistinguishable from that of th eir perforin-expressing littermates. The onset of disease was slightly dela yed. Brains of diseased perforin-deficient mice showed similar amounts and a similar distribution of CDS' T cells as wild-type animals. Perforin defic iency had no impact on the kinetics of viral spread through the CNS. Unlike brain lymphocytes from diseased wild-type mice, lymphocytes from perforin- deficient MRL mice showed no in vitro cytolytic activity towards target cel ls expressing the nucleoprotein of Borna disease virus. Taken together, the se results demonstrate that CD8(+) T cells mediate Borna disease independen t of perforin. They further suggest that the pathogenic potential of CNS-in filtrating CD8(+) T cells does not primarily reside in their lytic activity but rather in other functions.