A model of immune regulation as a consequence of randomized lymphocyte division and death times
A model of immune regulation as a consequence of randomized lymphocyte division and death times
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DOI：
10.1073/pnas.0700026104
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发表时间：
2007-03-20
影响因子：
11.1
通讯作者：
Hodgkin, P. D.
中科院分区：
文献类型：
--
作者：
Hawkins, E. D.;Turner, M. L.;Hodgkin, P. D.
适应性免疫反应的强度由淋巴细胞静止、增殖和凋亡的相互作用控制。淋巴细胞如何整合影响这些细胞命运的受体介导的信号是理解这个复杂系统的一个基本问题。我们研究了淋巴细胞如何交替分裂和死亡，以开发淋巴细胞生长调节的数学模型。该模型提供了一种强大的方法来拟合和分析荧光分裂跟踪数据，并揭示了总结受体介导的动力学变化如何逐步改变免疫反应，从快速耐受诱导到强免疫。我们的结果的一个重要结论是，在其他方面相同的细胞中的内在变异性（通常被视为噪音）可能已经进化成为免疫调节的一个基本特征。
The magnitude of an adaptive immune response is controlled by the interplay of lymphocyte quiescence, proliferation, and apoptosis. How lymphocytes integrate receptor-mediated signals influencing these cell fates is a fundamental question for understanding this complex system. We examined how lymphocytes interleave times to divide and die to develop a mathematical model of lymphocyte growth regulation. This model provides a powerful method for fitting and analyzing fluorescent division tracking data and reveals how summing receptor-mediated kinetic changes can modify the immune response progressively from rapid tolerance induction to strong immunity. An important consequence of our results is that intrinsic variability in otherwise identical cells, usually dismissed as noise, may have evolved to be an essential feature of immune regulation.