Prelog Martina, Keller Michael, Geiger Ralf, Brandstätter Anita, Würzner Reinhard, Schweigmann Ulrich, Zlamy Manuela, Zimmerhackl Lothar Bernd, Grubeck-Loebenstein Beatrix
Department of Pediatrics, Pediatrics I, Medical University Innsbruck, Anichstr. 35 A-6020 Innsbruck, Austria.
Clin Immunol. 2009 Feb;130(2):123-32. doi: 10.1016/j.clim.2008.08.023. Epub 2008 Oct 31.
The study was aimed to assess indicators of immunosenescence, such as the total counts of peripheral blood CD4(+)CD45RA(+)CD62L(+) (naive) T cells, the numbers of T cell receptor excision circles (TRECs), and Ki67-expression as marker of peripheral replication in thymectomized patients (TP) (n=101) compared to age-matched healthy donors (HD) (n=81). In TP, there was an inverse correlation between naive T cells and chronological age (p<0.001) or time post thymectomy (p<0.001). TP demonstrated lower TREC numbers in naive T cells compared to HD (p<0.001). TREC numbers negatively correlated with time post thymectomy (p<0.001). Percentages of Ki67-expresssing naive T cells were higher in TP compared to HD (p<0.05). The findings of the presented long-term follow up cohort of thymectomized patients indicate that changes of the peripheral naive T cell subset in TP may resemble the findings of an aging immune system in elderly persons after thymic involution. Our data provide evidence that peripheral T cell homeostasis in TP is maintained at minimal levels mainly by extrathymic expansion of existing naive T cells in the periphery to compensate the diminished thymic output.
本研究旨在评估免疫衰老指标，如外周血CD4(+)CD45RA(+)CD62L(+)（初始）T细胞的总数、T细胞受体切除环（TREC）的数量以及Ki67表达，后者作为胸腺切除患者（TP）（n = 101）外周复制的标志物，并与年龄匹配的健康供体（HD）（n = 81）进行比较。在TP中，初始T细胞与实际年龄（p<0.001）或胸腺切除术后时间（p<0.001）呈负相关。与HD相比，TP中初始T细胞的TREC数量较低（p<0.001）。TREC数量与胸腺切除术后时间呈负相关（p<0.001）。与HD相比，TP中表达Ki67的初始T细胞百分比更高（p<0.05）。本项对胸腺切除患者的长期随访队列研究结果表明，TP中外周初始T细胞亚群的变化可能类似于胸腺退化后老年人衰老免疫系统的表现。我们的数据提供了证据，表明TP中外周T细胞稳态主要通过外周现有初始T细胞的胸腺外扩增维持在最低水平，以补偿胸腺输出的减少。
