Nasi Milena, Troiano Leonarda, Lugli Enrico, Pinti Marcello, Ferraresi Roberta, Monterastelli Elena, Mussi Chiara, Salvioli Gianfranco, Franceschi Claudio, Cossarizza Andrea
Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia School of Medicine, via Campi 287, 41100 Modena, Italy.
Aging Cell. 2006 Apr;5(2):167-75. doi: 10.1111/j.1474-9726.2006.00204.x.
During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T-cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T-cell receptor rearrangement excision circles (TREC). A new method based upon real-time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six-color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7 receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long-living lymphocytes that have not yet encountered their antigen. IL-7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.
在衰老过程中，胸腺会经历显著的退化，这导致了T细胞区室的深刻变化。为了研究胸腺在人类寿命极限时产生新细胞的能力，我们分析了44位百岁老人外周T淋巴细胞更新和维持的一些基本机制。通过对呈现T细胞受体重排切除环（TREC）的细胞进行定量分析胸腺功能。我们采用了一种基于实时PCR的新方法，发现大多数百岁老人（84%）的TREC+细胞水平检测不到。六色细胞荧光分析显示，百岁老人的初始T细胞数量极少；中央记忆T细胞和效应记忆T细胞大幅增加，而终末分化细胞的数量与年轻（20 - 45岁）或中年（58 - 62岁）供体中的数量相同。酶联免疫吸附测定、流式细胞术和实时PCR结果表明，白细胞介素（IL）-7和IL-7受体α链（CD127）水平在所有年龄段均相同。然而，百岁老人女性的IL-7血浆水平高于男性。TREC+细胞和极少数初始T淋巴细胞的存在表明，在百岁老人中，这些细胞要么来源于胸腺淋巴细胞生成岛的残余物，要么甚至代表尚未接触其抗原的长寿淋巴细胞。IL-7可能是导致女性更有可能达到典型极端年龄的因素之一。
