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J. Exp. Med.,
Volume 187, Number 10, May 18, 1998 1575-1582
By
From the Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital,
Headington, Oxford OX3 9DU, United Kingdom
Mice intranasally inoculated with influenza A/X-31 are protected against a subsequent intracerebral challenge with the neurovirulent influenza A/WSN and this heterotypic protection is
mediated by CD8+ cytotoxic T lymphocytes. We have studied the kinetics of this secondary
immune response and found that despite the elimination of replication-competent virus by day
10, we were able to recover activated influenza-specific cytotoxic T lymphocytes (CTLs) that killed freshly ex vivo from the brains of mice for at least 320 d after the intracerebral inoculation. The activated antiviral CTLs expressed high levels of the early activation marker CD69, suggesting continuing TCR signaling despite a lack of viral protein and major histocompatibility complex staining by immunohistochemistry in the brain parenchyma and barely detectable
levels of viral nucleic acid by single and two-step reverse transcription PCR. Local persistence
of activated lymphocytes may be important for efficient long-term responses to viruses prone
to recrudesce in sites of relative immune privilege.
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