Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions.
Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions.
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DOI：
10.1016/j.smim.2011.10.002
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发表时间：
2011-12
影响因子：
7.8
通讯作者：
Tomoyuki Yamaguchi;J. Wing;S. Sakaguchi
中科院分区：
文献类型：
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作者：
Tomoyuki Yamaguchi;J. Wing;S. Sakaguchi
表达Foxp 3的调节性T细胞（TCRs）在维持免疫耐受和稳态中起着至关重要的作用。了解Treg免疫生物学的关键问题之一是确定它们如何抑制过度或异常的免疫反应。虽然已经报道了许多分子有助于Treg抑制功能，但每个分子的重要性和确切作用尚不清楚。在这篇综述中，我们提出并讨论了两种模式的抑制可以区分。在生理和稳定状态下，天然T细胞可以通过剥夺抗原反应性T细胞的活化信号（包括CD 28信号和IL-2）来抑制幼稚T细胞的活化，使后者在淋巴组织中保持幼稚状态。这些剥夺机制在炎症条件下被暂时废除，允许T细胞对抗原作出反应。相比之下，在高度炎症性环境中，例如在微生物感染中，活化的T细胞活化蛋白获得杀死或抑制效应T细胞和抗原呈递细胞的能力，例如通过颗粒酶/穿孔素形成和IL-10分泌，从而主动抑制过度的免疫应答。了解这些过程将有助于通过THBE有效地控制生理和病理免疫反应。
Foxp3-expressing regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance and homeostasis. One of the key issues for understanding Treg immunobiology is to determine how they suppress excessive or aberrant immune responses. Although a number of molecules have been reported to contribute to Treg suppressive function, the importance and precise role of each molecule is not clear. In this review, we propose and discuss that two modes of suppression can be distinguished. In the physiological and steady state, activation of naïve T cells can be suppressed by natural Tregs via deprivation of activation signals including CD28 signal and IL-2 from antigen-reactive T cells, keeping the latter in a naïve state in lymphoid tissues. These deprivation mechanisms are transiently abrogated in inflammatory conditions, allowing T cells to respond to antigen. In contrast, in highly inflammatory environments, for example, in microbial infection, activated Tregs acquire the capacity to kill or inactivate effector T cells and antigen-presenting cells, for example, via granzyme/perforin formation and IL-10 secretion, thereby actively damping excessive immune responses. Understanding these processes will help effectively controlling physiological and pathological immune responses via Tregs.