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© The Rockefeller University Press, 0022-1007/1998/5/1575/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1575-1582

Articles

Long-Term Persistence of Activated Cytotoxic T Lymphocytes after Viral Infection of the Central Nervous System

Simon Hawke, Philip G. Stevenson, Samantha Freeman, and Charles R.M. Bangham

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.

Key Words: immunity • virus • central nervous system • influenza virus • mouse

Address correspondence to S. Hawke, Division of Neuroscience and Psychological Medicine, Level 10E, Imperial College School of Medicine at Charing Cross, St. Dunstan's Rd., London W6 8RP, UK. Phone: 44-181-8467686; Fax: 44-181-8467715; E-mail: s.hawke{at}cxwms.ac.uk

P.G. Stevenson's current address is the Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN. C.R.M. Bangham's current address is the Department of Immunology, Imperial College School of Medicine at St. Mary's, Norfolk Place, London, UK.

Abbreviations used: CNS, central nervous system; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein.


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