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

Abstract

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.

• Authors: Georgia Deliyannis, Katherine Kedzierska, Yuk Fai Lau, Weiguang Zeng, Stephen J Turner, David C Jackson, Lorena E Brown
• Journal: European journal of immunology (Eur J Immunol) Vol. 36 Issue 3 Pg. 770-8 (Mar 2006) ISSN: 0014-2980 [Print] Germany
• PMID: 16435281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Influenza Vaccines
• Lipoproteins
• Vaccines, Synthetic
• Interferon-gamma

Topics

• Administration, Intranasal
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Epitopes, T-Lymphocyte (administration & dosage, immunology)
• Female
• Humans
• Immunologic Memory (immunology)
• Influenza A virus (immunology)
• Influenza Vaccines (administration & dosage, immunology)
• Influenza, Human (immunology, prevention & control)
• Interferon-gamma (immunology, metabolism)
• Lipoproteins (administration & dosage, immunology)
• Lung (immunology)
• Lymph Nodes (immunology)
• Mice
• Mice, Inbred BALB C
• Vaccines, Synthetic (administration & dosage, immunology)