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

• Published in: European journal of immunology 2006-03, Vol.36 (3), p.770-778
• Main Authors: Deliyannis, Georgia, Kedzierska, Katherine, Lau, Yuk Fai, Zeng, Weiguang, Turner, Stephen J., Jackson, David C., Brown, Lorena E.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - secretion; Epitopes, T-Lymphocyte - administration & dosage; Epitopes, T-Lymphocyte - immunology; Female; Humans; Immunologic Memory - immunology; Influenza; Influenza A virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Interferon-gamma - immunology; Interferon-gamma - secretion; Lipopeptide; Lipoproteins - administration & dosage; Lipoproteins - immunology; Lung; Lung - immunology; Lymph Nodes - immunology; Mice; Mice, Inbred BALB C; T cells; Vaccination; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200535217

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‐γ‐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.