Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response.
Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response.
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DOI：
10.1038/msb.2010.90
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发表时间：
2010-11-30
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
了解免疫系统如何在耐受和抗原激活之间做出决定，需要将细胞因子调节作为一个高度动态的过程。我们通过结合计算机模拟和体外单细胞测量，定量了免疫应答期间T细胞群体中白细胞介素-2（IL-2）信号传导的动态。我们证明，IL-2受体表达水平在T细胞中变化很大，从而在单个细胞消耗、产生和参与群体内IL-2信号传导的能力中产生很大的变异性。我们的模型揭示，在群体水平上，这些异质细胞参与调节性（Treg）和效应性（Teff）T细胞之间的IL-2拔河，由此获得IL-2可以增加Teff细胞的存活或Treg细胞的抑制能力。这种拔河是在系统水平上执行Treg细胞的核心功能的机制，即特异性抑制弱活化的Teff细胞的存活信号，但不抑制强活化的细胞的存活信号。我们的综合模型产生了定量的，实验验证的预测Treg抑制的操纵。
Understanding how the immune system decides between tolerance and activation by antigens requires addressing cytokine regulation as a highly dynamic process. We quantified the dynamics of interleukin-2 (IL-2) signaling in a population of T cells during an immune response by combining in silico modeling and single-cell measurements in vitro. We demonstrate that IL-2 receptor expression levels vary widely among T cells creating a large variability in the ability of the individual cells to consume, produce and participate in IL-2 signaling within the population. Our model reveals that at the population level, these heterogeneous cells are engaged in a tug-of-war for IL-2 between regulatory (Treg) and effector (Teff) T cells, whereby access to IL-2 can either increase the survival of Teff cells or the suppressive capacity of Treg cells. This tug-of-war is the mechanism enforcing, at the systems level, a core function of Treg cells, namely the specific suppression of survival signals for weakly activated Teff cells but not for strongly activated cells. Our integrated model yields quantitative, experimentally validated predictions for the manipulation of Treg suppression.
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影响因子：
4.4
作者：
Kemp, Melissa L.;Wille, Lucia;Lauffenburger, Douglas A.
通讯作者：
Lauffenburger, Douglas A.
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作者：
CANTRELL, DA;SMITH, KA
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SMITH, KA
影响因子：
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通讯作者：
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影响因子：
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作者：
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DAUTRYVARSAT, A