title: Immunodominant peptides from conserved influenza proteins--a tool for more efficient vaccination in the elderly?
abstract: Influenza-specific CD8+ T cells are important for the clearance of infection especially in high risk groups such as elderly persons. Activation of these cells by immunization might therefore be a useful tool for a better protection of this specific age group. We therefore analyzed the frequency, phenotype and function of CD8+ T cells with specificity to the influenza M1(58-66) peptide in young, middle-aged and elderly persons ex vivo and after in vitro stimulation. Significantly lower numbers of M1(58-66)-specific CD8+ T cells were detected in the middle-aged and elderly compared to young donors. M1(58-66)-specific CD8+ T cells were either CD45RA(low)CD45RO(low) or CD45RA-CD45RO+, expressed CD28 and CD62L and did not produce perforin. There was no difference in the phenotype of influenza-specific CD8+ T cells between the three age groups. Despite the initially low numbers of M1(58-66)-specific CD8+ T cells in the older age groups, these cells could be expanded in vitro following peptide stimulation. They also acquired a CD45RO+CD28+ CD62L(+/-) phenotype and produced perforin. Our results demonstrate that although initially low in number, M1(58-66)-specific CD8+ T cells from elderly persons can be propagated and differentiated into perforin producing effector cells upon appropriate stimulation. M1(58-66) peptide or other immunodominant peptides derived from conserved influenza proteins could therefore be useful in future influenza vaccines in order to render elderly persons better protected against disease, in particular in the case of an influenza pandemic.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Dietmar
authors.initials: D
authors.lastname: Herndler-Brandstetter
authors.forename: Sandra Vega
authors.initials: SV
authors.lastname: Chaparro
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jenewein
authors.forename: Michael
authors.initials: M
authors.lastname: Keller
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D014611:Vaccination / Q000639:trends*; D022223:Vaccines, Subunit / Q000276:immunology* / Q000627:therapeutic use; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D054353:Perforin; D017493:Leukocyte Common Antigens