Mathematical Modeling Reveals the Biological Program Regulating Lymphopenia-Induced Proliferation1
Mathematical Modeling Reveals the Biological Program Regulating Lymphopenia-Induced Proliferation1
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数学模型揭示了调节淋巴细胞减少引起的增殖的生物程序1
DOI：
10.4049/jimmunol.180.3.1414
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
B. Seddon
中科院分区：
文献类型：
--
作者：
A. Yates;M. Saini;A. Mathiot;B. Seddon
TCR对肽-MHC的识别诱导T淋巴细胞进行细胞分裂。虽然识别外来肽诱导细胞分裂和分化的程序由响应T细胞，刺激自身肽MHC复合物在淋巴细胞减少的条件下诱导一个较慢的爆发分裂，可能会或可能不会伴随效应分化。虽然这两种反应都是由TCR的信号触发的，但尚不清楚它们是否代表了不同的细胞周期控制程序。在这项研究中，我们使用数学建模的方法来分析TCR转基因F5 T细胞对淋巴细胞减少症的增殖反应。我们测试了两种根本不同的细胞分裂模型：一种是T细胞被触发进入“自动驾驶仪”确定性分裂爆发，一种模型在其他地方成功地用于描述T细胞对同源Ag的反应，另一种是细胞进行独立的单次随机分裂的对比模型。尽管自动驾驶仪模型对F5 T细胞对淋巴细胞减少症的反应提供了非常差的描述，但单一随机分裂的模型非常接近实验数据。此外，该模型被证明是稳健的，因为该模型对细胞行为的具体预测，包括分裂的开始、速率和性质，都成功地通过实验验证。我们的研究结果表明，淋巴细胞减少诱导的细胞分裂涉及一个过程中的单一随机分裂，这是最适合的稳态，而不是分化的作用。
Recognition of peptide-MHC by the TCR induces T lymphocytes to undergo cell division. Although recognition of foreign peptide induces a program of cellular division and differentiation by responding T cells, stimulation by self-peptide MHC complexes in lymphopenic conditions induces a slower burst of divisions that may or may not be accompanied by effector differentiation. Although both responses are triggered by signals from the TCR, it is not known whether they represent distinct programs of cell cycle control. In this study, we use a mathematical modeling approach to analyze the proliferative response of TCR transgenic F5 T cells to lymphopenia. We tested two fundamentally different models of cell division: one in which T cells are triggered into an “autopilot” deterministic burst of divisions, a model successfully used elsewhere to describe T cell responses to cognate Ag, and a second contrasting model in which cells undergo independent single stochastic divisions. Whereas the autopilot model provided a very poor description of the F5 T cell responses to lymphopenia, the model of single stochastic divisions fitted the experimental data remarkably closely. Furthermore, this model proved robust because specific predictions of cellular behavior made by this model concerning the onset, rate, and nature of division were successfully validated experimentally. Our results suggest cell division induced by lymphopenia involves a process of single stochastic divisions, which is best suited to a homeostatic rather than differentiation role.
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影响因子：
30.5
作者：
Kaech, SM;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
2
作者：
Antia, R;Bergstrom, CT;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1073/pnas.0407417101
发表时间：
2004-11-30
影响因子：
11.1
作者：
Goldrath, AW;Luckey, CJ;Mathis, D
通讯作者：
Mathis, D
DOI：
10.1073/pnas.98.4.1728
发表时间：
2001-02-13
影响因子：
11.1
作者：
Ge, Q;Rao, VP;Chen, JZ
通讯作者：
Chen, JZ