Cossarizza A, Ortolani C, Paganelli R, Barbieri D, Monti D, Sansoni P, Fagiolo U, Castellani G, Bersani F, Londei M, Franceschi C
Dipartimento di Scienze Biomediche, University of Modena, Italy.
Mech Ageing Dev. 1996 Mar 29;86(3):173-95. doi: 10.1016/0047-6374(95)01691-0.
CD4+ and CD8+ peripheral blood T lymphocytes show mutually exclusive expression of CD45RA or CD45R0, two isoforms of the common leukocyte antigen that seem to recognize so-called virgin/unprimed and memory/activated T cells. The expression of these isoforms has been studied by three colour cytofluorimetric analysis on CD4+ or CD8+ peripheral blood CD3+ cells from 22 healthy centenarians, analyzed in a context of 202 healthy donors 0-110 years old. An age-related unbalance of virgin and memory cells was found between CD4+ and CD8+ subsets. As expected, at birgh 95-99% of the CD3+ lymphocytes expressed the CD45RA isoform. A rapid increase of CD45R0+ cells was observed in the first 2-3 decades of life, this phenomenon being much more pronounced on CD4+ cells. Subsequently, the increase of the 'memory' compartment was much less rapid, so that in centenarians a consistent reservoire of CD45RA+ among CD4+ cells was still present (about 20%). In these exceptional individuals the percentage of CD45RA+ cells among CD8+ T lymphocytes was even higher (about 50%), and only slightly lower than that of young donors (about 55-60%). Thus, the main changes occurred at a different rate in CD4+ (about 20%). In these exceptional individuals the percentage of CD45RA+ cells among CD8+ T lymphocytes was even higher (about 50%), and only slightly lower than that of young donors (about 55-60%). Thus, the main changes occurred at a different rate in CD4+ and in CD8+ T cells, at an age of between 0 and 30 years, when the thymus is still functionally active. Interestingly, no difference in the usage of CD45 isoforms was observed within T cells bearing four different V beta-T cell receptor (TCR). The significance of this age-related unbalance is unknown. However, the presence of a great number of CD45RA+ T lymphocytes within the CD4+ and the CD8+ T cell subsets even in the peripheral blood of centenarians poses the problem of their origin (thymus? extrathymic sites?), of their functional role and of their lifespan. Moreover, the data on centenarians suggest that they may represent a very selected population where a slowing of immunosenescence occurs.
CD4⁺和CD8⁺外周血T淋巴细胞呈现CD45RA或CD45R0的互斥性表达，这是常见白细胞抗原的两种同种型，似乎可识别所谓的初始/未致敏T细胞和记忆/活化T细胞。通过三色细胞荧光分析对来自22名健康百岁老人的CD4⁺或CD8⁺外周血CD3⁺细胞中这些同种型的表达进行了研究，并与202名0至110岁的健康供者进行了对比分析。在CD4⁺和CD8⁺亚群之间发现了与年龄相关的初始细胞和记忆细胞失衡。正如预期的那样，在出生时95 - 99%的CD3⁺淋巴细胞表达CD45RA同种型。在生命的最初2 - 3个十年中观察到CD45R0⁺细胞迅速增加，这种现象在CD4⁺细胞上更为明显。随后，“记忆”亚群的增加速度要慢得多，以至于在百岁老人中，CD4⁺细胞中仍存在相当数量的CD45RA⁺细胞（约20%）。在这些特殊个体中，CD8⁺T淋巴细胞中CD45RA⁺细胞的百分比甚至更高（约50%），仅略低于年轻供者（约55 - 60%）。因此，主要变化在CD4⁺（约20%）和CD8⁺T细胞中以不同的速率发生。在这些特殊个体中，CD8⁺T淋巴细胞中CD45RA⁺细胞的百分比甚至更高（约50%），仅略低于年轻供者（约55 - 60%）。因此，主要变化在CD4⁺和CD8⁺T细胞中以不同的速率发生，发生在0至30岁之间，此时胸腺仍具有功能活性。有趣的是，在携带四种不同Vβ - T细胞受体（TCR）的T细胞内未观察到CD45同种型使用的差异。这种与年龄相关的失衡的意义尚不清楚。然而，即使在百岁老人的外周血中，CD4⁺和CD8⁺T细胞亚群内存在大量CD45RA⁺T淋巴细胞，这就带来了它们的起源（胸腺？胸腺外部位？）、功能作用和寿命的问题。此外，关于百岁老人的数据表明，他们可能代表了一个免疫衰老减缓的非常特殊的人群。
