Quorum-Sensing in CD4(+) T Cell Homeostasis: A Hypothesis and a Model.
Quorum-Sensing in CD4(+) T Cell Homeostasis: A Hypothesis and a Model.
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CD4（+）T细胞稳态中的Quorum-Sensing：一种假设和模型。
DOI：
10.3389/fimmu.2012.00125
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发表时间：
2012
影响因子：
7.3
通讯作者：
Freitas AA
中科院分区：
文献类型：
--
作者：
Almeida AR;Amado IF;Reynolds J;Berges J;Lythe G;Molina-París C;Freitas AA
淋巴细胞数量的稳态被认为是由于细胞群体之间对有限大小的共同小生境的竞争，由相互作用和细胞存活所需的营养因子的组合定义。在这里，我们提出了一个新的机制：淋巴细胞数量的稳态也可以通过淋巴细胞感知其自身种群密度的能力来实现。这种机制会让人想起细菌使用的原始群体感应系统，其中一些细菌感知到由群体中其他元素分泌的细菌代谢物的积累，使它们能够“计数”存在的细胞数量并相应地调整它们的生长。我们认为，CD 4 + T细胞数量的稳态可能通过类群体感应机制发生，其中IL-2由活化的CD 4 + T细胞产生，并由表达高亲和力IL-2 R α链的CD 4 + Treg细胞群体感应，并可调节活化的产生IL-2的CD 4 + T细胞和总CD 4 + T细胞群体的数量。换句话说，CD 4 + T细胞群可以通过监测活化细胞的数量来抑制它们的生长，从而防止免疫应答期间不受控制的淋巴细胞增殖。我们推测，这种群体感应机制的故障可能会导致不受控制的T细胞活化和自身免疫。最后，我们提出了一个数学模型，描述了在免疫反应过程中的CD 4 + T细胞稳态的IL-2和群体感应机制的关键作用。
Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum-sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to “count” the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+ T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the key role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.