Hawkins E D, Turner M L, Dowling M R, van Gend C, Hodgkin P D
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5032-7. doi: 10.1073/pnas.0700026104. Epub 2007 Mar 14.
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.
适应性免疫反应的强度由淋巴细胞的静止、增殖和凋亡之间的相互作用所控制。淋巴细胞如何整合影响这些细胞命运的受体介导信号，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错划分分裂和死亡时间，以建立一个淋巴细胞生长调节的数学模型。该模型为拟合和分析荧光分裂追踪数据提供了一种强大的方法，并揭示了将受体介导的动力学变化相加如何能从快速诱导耐受逐渐改变为强大的免疫反应。我们结果的一个重要结论是，通常被视为噪声的原本相同细胞中的内在变异性，可能已进化成为免疫调节的一个基本特征。
