Successful and Maladaptive T Cell Aging.
Successful and Maladaptive T Cell Aging.
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DOI：
10.1016/j.immuni.2017.03.010
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发表时间：
2017-03-21
期刊：
影响因子：
32.4
通讯作者：
Weyand CM
中科院分区：
文献类型：
--
作者：
Goronzy JJ;Weyand CM
在整个生命过程中，T细胞系统适应不断变化的资源和需求，导致老年人的免疫系统从根本上重建。在这里，我们回顾了老年免疫系统的细胞和分子特征，并讨论了这些适应性机制固有的权衡。过程包括以干细胞部分丧失和不完全分化为代价维持区室大小的稳态增殖，以及抑制效应T细胞扩增并防止寡克隆性增加但也干扰记忆细胞生成的负调控程序的激活。我们提出，免疫失败发生时，老化的T细胞系统开发的适应性策略失败，并讨论如何，在某些情况下，与T细胞老化相关的程序最终在适应不良反应，直接导致慢性炎症性疾病。
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation. We propose that immune failure occurs when adaptive strategies developed by the aging T cell system fail and also discuss how, in some settings, the programs associated with T cell aging culminates in a maladaptive response that directly contributes to chronic inflammatory disease.