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

Georgia Deliyannis, Katherine Kedzierska, Yuk Fai Lau, Weiguang Zeng, Stephen J. Turner, David C. Jackson, Lorena E. Brown

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63 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)770-778
Number of pages9
JournalEuropean Journal of Immunology
Volume36
Issue number3
DOIs
Publication statusPublished - 1 Mar 2006
Externally publishedYes

Keywords

  • Influenza
  • Lipopeptide
  • Lung
  • T cells
  • Vaccination

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