Zusammenfassung
Influenza-spezifische zytotoxische CD8+ T-Zellen stellen einen wesentlichen Bestandteil bei der Überwindung einer Infektion dar, insbesondere in Hochrisikogruppen wie älteren Personen. Eine Aktivierung dieser Zellen durch eine Impfung wäre deshalb eine wichtige Voraussetzung um einen besseren Schutz für diese Altersgruppe zu erreichen. Deshalb haben wir die Häufigkeit, den Phänotyp und die Funktion von Influenza M158–66 Peptid-spezifischen CD8+ T-Zellen in drei verschiedenen Altersgruppen (27 ± 1 Jahre; 46 ± 3 Jahre und 72 ± 2 Jahre) ex vivo und nach in vitro Stimulation untersucht. Bei Personen ab einem Alter von 38 Jahren stellten wir eine geringere Anzahl von M158–66-spezifischen CD8+ T-Zellen fest. Diese Zellen exprimierten CD28, CD62L und waren entweder CD45RAlowCD45ROlow oder CD45RA-CD45RO+, produzierten aber kein Perforin. Kein Unterschied zeigte sich beim Phänotyp von Influenza-spezifischen CD8+ T-Zellen zwischen den drei Altersgruppen. Trotz der zu Beginn geringen Anzahl von M158–66-spezifischen CD8+ T-Zellen in älteren Personen, konnte diese Population nach in vitro Stimulation mit dem M158–66-Peptid signifikant vergrößert werden. Diese M158–66-spezifische CD8+ T-Zellen produzierten Perforin und hatten einen CD45RO+CD28+CD62L+/− Phänotyp. Unsere Ergebnisse zeigen, dass trotz einer geringen Anzahl M158–66-spezifischer CD8+ T-Zellen bei älteren Personen, diese Zellen nach in vitro Stimulation mit einem Peptid gut expandieren und in Perforin-produzierende Effektor-T-Zellen differenzierbar sind. M158–66-Peptid oder andere immundominante Peptide aus konservierten Influenzaproteinen könnten somit einen wichtigen Bestandteil zukünftiger Influenzaimpfstoffe darstellen um älteren Personen einen verbesserten Schutz vor Influenza zu bieten, insbesondere beim Auftreten einer Influenza Pandemie.
Summary
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 M158–66 peptide in young, middle-aged and elderly persons ex vivo and after in vitro stimulation. Significantly lower numbers of M158–66-specific CD8+ T cells were detected in the middle-aged and elderly compared to young donors. M158–66-specific CD8+ T cells were either CD45RAlowCD45ROlow 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 M158–66-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, M158–66-specific CD8+ T cells from elderly persons can be propagated and differentiated into perforin producing effector cells upon appropriate stimulation. M158–66 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 pandemia.
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Almanzar, G., Herndler-Brandstetter, D., Chaparro, S. et al. Immunodominant peptides from conserved influenza proteins – A tool for more efficient vaccination in the elderly?. Wien Med Wochenschr 157, 116–121 (2007). https://doi.org/10.1007/s10354-007-0393-y
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DOI: https://doi.org/10.1007/s10354-007-0393-y