3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance
3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance
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DOI：
10.1038/sj.icb.7100023
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Cooley, Margaret
中科院分区：
文献类型：
--
作者：
Jansson, Andreas;Harlen, Mikael;Cooley, Margaret
Th细胞发育被认为包括选择性机制，其中某些细胞因子选择Th 1或Th 2细胞增殖和生长。选择性理论是基于这样的观察，即Th 2细胞分泌IL-4，一种促进Th 2发育的细胞因子，而Th 1细胞分泌有利于Th 1发育的干扰素-γ（IFN-γ），并且已经提出积极和消极的选择性影响都起作用。在这项研究中，我们调查的作用，自分泌分泌和利用IL-4的Th 2细胞和解决的问题，是否激活的Th 2细胞可以积极选择从其他Th 2细胞分泌的IL-4。我们提出了一个空间三维（3D）建模方法来模拟IL-4配体和IL-4受体表达的离散IL-4分泌细胞之间的相互作用。基于IL-4受体-配体系统的现有实验数据的模拟说明了Th细胞的发育如何高度依赖于正在通信的细胞之间的距离。该模型表明，单个Th 2细胞可能与约100 μ m范围内的可能的靶细胞通信，并且活化的Th 2细胞设法填充其自身的大部分IL-4受体，即使在低分泌速率下。该模型的预测表明，对Th 1细胞的负选择比IL-4的正选择更有效地促进Th 2优势。
Th-cell development has been suggested to include selective mechanisms in which certain cytokines select either Th1 or Th2 cells to proliferate and grow. The selective theory is based on the observation that Th2 cells secrete IL-4, a cytokine that promotes Th2 development, whereas Th1 cells secrete interferon-gamma (IFN-gamma) that favours Th1 development, and both positive and negative selective influences have been suggested to operate. In this study, we investigate the role of autocrine secretion and utilization of IL-4 by Th2 cells and address the question of whether an activated Th2 cell can be positively selected by IL-4 secreted from other Th2 cells. We present a spatial three dimensional (3D) modelling approach to simulate the interaction between the IL-4 ligand and its IL-4 receptors expressed on discrete IL-4 secreting cells. The simulations, based on existing experimental data on the IL-4 receptor-ligand system, illustrate how Th-cell development is highly dependent on the distance between cells that are communicating. The model suggests that a single Th2 cell is likely to communicate with possible target cells within a range of approximately 100 mu m and that an activated Th2 cell manages to fill most of its own IL-4 receptors, even at a low secretion rate. The predictions made by the model suggest that negative selection against Th1 cells is more effective than positive selection by IL-4 for promoting Th2 dominance.