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Journal of Virology, November 2001, p. 10460-10466, Vol. 75, No. 21
Abteilung Virologie, Institut für
Medizinische Mikrobiologie und Hygiene, Universität Freiburg,
D-79104 Freiburg, Germany
Received June 4 2001/Accepted 8 August 2001
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.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.21.10460-10466.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
CD8+ T Lymphocytes Mediate Borna
Disease Virus-Induced Immunopathology Independently of
Perforin
*
Corresponding author. Mailing address: Department of
Virology, University of Freiburg, Hermann-Herder-Str. 11, D-79104
Freiburg, Germany. Phone: 49-761-203-6622. Fax: 49-761-203-6562. E-mail: hausmann{at}ukl.uni-freiburg.de.
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