Steger M M, Maczek C, Grubeck-Loebenstein B
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria.
Mech Ageing Dev. 1997 Feb;93(1-3):125-30. doi: 10.1016/s0047-6374(96)01835-0.
Dendritic cells (DC) are professional antigen presenting cells which are essential for the initiation of an immune response. Recently we demonstrated that DC, which had been propagated from the peripheral blood of healthy elderly people, were morphologically and functionally intact. It was the aim of the present study to analyze how DC from young and old healthy individuals could affect T cell responsiveness to antigen in an in vitro senescence model. Tetanus toxoid (TT)-specific T cell lines were derived from 3 young (< 30 years) and 3 old (> 65 years) individuals and were kept in long term culture. T cell proliferation in response to stimulation with antigen presented by either autologous peripheral blood mononuclear cells (PBMC) or DC was assessed at three different time points, once soon after the initiation of the cultures and twice after 20 to 30 population doublings at a stage when growth, was slow and programmed cell death imminent. Antigen presentation by DC enhanced T cell proliferation at each time point and reinduced proliferation in in vitro aged T cell populations which had stopped dividing. Terminal apoptosis was thus prevented. DC from old individuals were as effective as cells from young donors. Our results demonstrate that DC stimulate the clonal expansion and postpone the clonal elimination of antigen-specific T cell populations. As a consequence they may increase immunoreactivity, prolong immunological memory and be of particular importance for the maintenance of the T cell repertoire in old age.
树突状细胞(DC)是专业的抗原呈递细胞,对免疫反应的启动至关重要。最近我们证明,从健康老年人外周血中培养出来的DC在形态和功能上都是完整的。本研究的目的是在体外衰老模型中分析年轻和年老健康个体的DC如何影响T细胞对抗原的反应性。破伤风类毒素(TT)特异性T细胞系来源于3名年轻(<30岁)和3名年老(>65岁)个体,并进行长期培养。在三个不同时间点评估T细胞对自体外周血单个核细胞(PBMC)或DC呈递的抗原刺激的增殖情况,一次是在培养开始后不久,另外两次是在培养20至30次群体倍增后,此时生长缓慢且程序性细胞死亡即将发生。在每个时间点,DC的抗原呈递都增强了T细胞的增殖,并在已停止分裂的体外老化T细胞群体中重新诱导了增殖。从而防止了终末凋亡。老年个体的DC与年轻供体的细胞一样有效。我们的结果表明,DC刺激抗原特异性T细胞群体的克隆扩增并推迟其克隆清除。因此,它们可能会增加免疫反应性,延长免疫记忆,并且对于老年期T细胞库的维持尤为重要。