Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France.
J Exp Med. 2013 Nov 18;210(12):2707-20. doi: 10.1084/jem.20122759.
Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of interleukin-2 (IL-2)-producing CD4(+) T cell (IL-2p) pool using different IL-2 reporter mice. We found that in the absence of either IL-2 or regulatory CD4(+) T (T reg) cells, the number of IL-2p cells increases. Administration of IL-2 decreases the number of cells of the IL-2p cell subset and, pertinently, abrogates their ability to produce IL-2 upon in vivo cognate stimulation, while increasing T reg cell numbers. We propose that control of the IL-2p cell numbers occurs via a quorum sensing-like feedback loop where the produced IL-2 is sensed by both the activated CD4(+) T cell pool and by T reg cells, which reciprocally regulate cells of the IL-2p cell subset. In conclusion, IL-2 acts as a self-regulatory circuit integrating the homeostasis of activated and T reg cells as CD4(+) T cells restrain their growth by monitoring IL-2 levels, thereby preventing uncontrolled responses and autoimmunity.
许多细菌物种利用群体感应来感知分泌代谢物的数量，并根据其种群密度来适应生长。我们想知道类似的机制是否会在淋巴细胞稳态中发挥作用。我们使用不同的白细胞介素-2（IL-2）报告小鼠研究了调节产生白细胞介素-2（IL-2）的 CD4(+) T 细胞（IL-2p）池大小的调控机制。我们发现，在缺乏 IL-2 或调节性 CD4(+) T（Treg）细胞的情况下，IL-2p 细胞的数量会增加。IL-2 的给药会减少 IL-2p 细胞亚群的细胞数量，并且特别地，消除了它们在体内同源刺激下产生 IL-2 的能力，同时增加了 Treg 细胞的数量。我们提出，IL-2p 细胞数量的控制是通过一种群体感应样的反馈回路发生的，其中产生的 IL-2 被激活的 CD4(+) T 细胞池和 Treg 细胞感知，Treg 细胞反过来调节 IL-2p 细胞亚群的细胞。总之，IL-2 作为一个自我调节回路，整合了激活和 Treg 细胞的稳态，因为 CD4(+) T 细胞通过监测 IL-2 水平来抑制其生长，从而防止不受控制的反应和自身免疫。
