CD8+ T Lymphocytes Mediate Borna Disease Virus-Induced Immunopathology Independently of Perforin
AUTOR(ES)
Hausmann, Jürgen
FONTE
American Society for Microbiology
RESUMO
Perforin-mediated lysis of target cells is the major antiviral effector mechanism of CD8+ T lymphocytes. We have analyzed the role of perforin in a mouse model for CD8+ T-cell-mediated central nervous system (CNS) immunopathology induced by Borna disease virus. When a defective perforin gene was introduced into the genetic background of the Borna disease-susceptible mouse strain MRL, the resulting perforin-deficient mice developed strong neurological disease in response to infection indistinguishable from that of their perforin-expressing littermates. The onset of disease was slightly delayed. Brains of diseased perforin-deficient mice showed similar amounts and a similar distribution of CD8+ T cells as wild-type animals. Perforin deficiency 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 cells expressing the nucleoprotein of Borna disease virus. Taken together, these results demonstrate that CD8+ T cells mediate Borna disease independent of perforin. They further suggest that the pathogenic potential of CNS-infiltrating CD8+ T cells does not primarily reside in their lytic activity but rather in other functions.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=114620Documentos Relacionados
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