Long-term persistence of activated cytotoxic T lymphocytes after viral infection of the central nervous system.
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.
Hawke
S
S
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom. s.hawke@cxwms.ac.uk
Stevenson
P G
PG
Freeman
S
S
Bangham
C R
CR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013997:Time Factors