Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 7, Pages 1855-1863Publisher
WILEY
DOI: 10.1002/eji.200737196
Keywords
CD8+T cells; infectious diseases; virology; west nile; virus
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Funding
- NCRR NIH HHS [RR0163, P51 RR000163] Funding Source: Medline
- NIAID NIH HHS [N01AI50027, T32 AI007472] Funding Source: Medline
- PHS HHS [N01 50027] Funding Source: Medline
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West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the Flaviviridae genus, which causes lethal encephalitis in a subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and mortality, but the basis of this effect is unclear, and the molecular and cellular parameters of the host-WNV infection are just beginning to be elucidated. Indeed, numerous mechanisms were implicated in protection in vivo against WNV (IFN-I and IFN-gamma, antibody, C', CD8 and CD4 T cells), but the individual importance of each one of these remains unclear. Here, we show that transfer of highly enriched naive CD8(+) T cells protects the majority of alymphoid mice against lethal WNV infection. To substantiate and expand this finding, we defined the peptide specificity of the CD8 response in H-2b mice and used a panel of identified peptides to map one dominant (NS4b (2248-2256)) and several subdominant epitopes. The hierarchy of these epitopes was stably maintained in the memory responses. Most importantly, CTL lines directed against these peptides conferred protection against lethal WNV infection in direct proportion to the epitope immunodominance. These results provide a springboard for future characterization of T cell responses against WNV and demonstrate, for the first time, that CD8 T cells can single-handedly protect from this disease.
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