Almanzar Giovanni, Herndler-Brandstetter Dietmar, Chaparro Sandra Vega, Jenewein Brigitte, Keller Michael, Grubeck-Loebenstein Beatrix
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
Wien Med Wochenschr. 2007;157(5-6):116-21. doi: 10.1007/s10354-007-0393-y.
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.
流感特异性CD8+ T细胞对于清除感染非常重要,尤其是在老年人等高风险人群中。因此,通过免疫激活这些细胞可能是更好地保护这一特定年龄组的有用工具。我们因此在体外和体外刺激后,分析了年轻人、中年人和老年人中对流感M1(58 - 66)肽具有特异性的CD8+ T细胞的频率、表型和功能。与年轻供体相比,在中年人和老年人中检测到的M1(58 - 66)特异性CD8+ T细胞数量显著减少。M1(58 - 66)特异性CD8+ T细胞要么是CD45RA(low)CD45RO(low),要么是CD45RA - CD45RO+,表达CD28和CD62L,并且不产生穿孔素。三个年龄组之间流感特异性CD8+ T细胞的表型没有差异。尽管老年组中最初M1(58 - 66)特异性CD8+ T细胞数量较少,但这些细胞在肽刺激后可在体外扩增。它们还获得了CD45RO+CD28+ CD62L(+/-)表型并产生穿孔素。我们的结果表明,尽管老年人的M1(58 - 66)特异性CD8+ T细胞最初数量较少,但在适当刺激下可以增殖并分化为产生穿孔素的效应细胞。因此,M1(58 - 66)肽或其他源自保守流感蛋白的免疫显性肽可能对未来的流感疫苗有用,以便使老年人更好地预防疾病,特别是在流感大流行的情况下。