Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates
Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates
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DOI：
10.1073/pnas.0705905104
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Nikolich-Zugich, Janko
中科院分区：
文献类型：
--
作者：
Cicin-Sain, Luka;Messaoudi, Ilhem;Nikolich-Zugich, Janko
幼稚T细胞的丧失是免疫老化的标志。虽然胸腺退化是这种幼稚T细胞损失的主要驱动因素，但对衰老灵长类动物中幼稚T细胞耗竭的其他机制的贡献知之甚少。我们研究了衰老恒河猴（RM）不同T细胞亚群的稳态循环和增殖扩张的作用。BrdU掺入和G（1）-M标记物Ki-67的表达在外周初始CD 4中升高，在老年人而不是年轻成人RM的初始CD 8 T细胞中甚至更明显。衰老的幼稚细胞不会在老年动物中积累。相反，初始CD 8 T细胞区室的相对大小与其增殖速率呈负相关。同样，在具有升高的初始CD 8 T细胞增殖的个体中，T细胞受体多样性降低。这一明显的矛盾是由一个显着增加营业额伴随着幼稚池的损失。当初始CD 8 T细胞池降低到低于总血液CD 8细胞的4%时，周转率呈指数增加。这些结果将幼稚T细胞池的缩小与稳态周转的急剧增加联系起来，这有可能加剧幼稚池的进行性耗竭并收缩T细胞库。因此，稳态T细胞增殖表现出时间拮抗多效性，有利于成年期的T细胞维持，但不利于衰老个体的长期T细胞维持。
The loss of naive T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naive T cell loss, less is known about the contribution of other mechanisms to the depletion of naive T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G(1)-M marker Ki-67 were elevated in peripheral naive CD4 and even more markedly in the naive CD8 T cells of old, but not young adult, RM. Proliferating naive cells did not accumulate in old animals. Rather, the relative size of the naive CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naive CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naive pool loss. The turnover increased exponentially when the naive CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naive T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naive pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.