Intranasal lipopeptide primes lung-resident memory CD8+ T cells for long-term pulmonary protection against influenza.
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-[2,3-bis(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.
Deliyannis
Georgia
G
The Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia.
Kedzierska
Katherine
K
Lau
Yuk Fai
YF
Zeng
Weiguang
W
Turner
Stephen J
SJ
Jackson
David C
DC
Brown
Lorena E
LE
D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008074:Lipoproteins / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; D008074:Lipoproteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma