Intranasal lipopeptide primes lung-resident memory CD8+ T cells for long-term pulmonary protection against influenza

被引:66
作者
Deliyannis, G
Kedzierska, K
Lau, YF
Zeng, WG
Turner, SJ
Jackson, DC
Brown, LE [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3010, Australia
[2] VacTX Pty Ltd, Hawthorn, Vic, Australia
关键词
influenza; lipopeptide; lung; T cells; vaccination;
D O I
10.1002/eji.200535217
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The longevity of the influenza virus-specific CD8(+) T cell response following intranasal delivery of a synthetic lipopeptide was investigated and the characteristics and location of the cells associated with viral clearance examined. The lipopeptide, incorporating an epitope for CD8(+) T cells and another for CD4(+) T cells with the lipid moiety S-[2,3bis(palmitoyloxy)propyl]cysteine (Pam2Cys) attached, induced potent and long-lived pulmonary protection. Both the lipopeptide and its largely unprotective non-lipidated counterpart elicited comparable numbers of CD8(+) T cells in the spleen, which was the main location of the memory pool. However, the lipopeptide, unlike the non-lipidated peptide, also induced a substantial memory population that remained in the lungs and was rapidly activated upon viral challenge months later. These lipopeptide-induced lung-resident CD8(+) T cells were also very similar in number and IFN-gamma-secreting potential to those induced by prior exposure to the virus itself and are likely mediators of initial viral clearance prior to recruitment from the expanding lymph node T cell pool. Significant clearing responses were demonstrated as late as 9 months post-lipopeptide vaccination. This study shows that CD8(+) T cells primed by the lipopeptide are not only long-lived but can take up residence in the lung where they are important early mediators of pulmonary protection.
引用
收藏
页码:770 / 778
页数:9
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