Two-compartment model of NK cell proliferation: insights from population response to IL-15 stimulation.
Two-compartment model of NK cell proliferation: insights from population response to IL-15 stimulation.
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DOI：
10.4049/jimmunol.1102989
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
French AR
中科院分区：
文献类型：
--
作者：
Zhao YM;French AR
自然杀伤(NK)细胞是一种先天淋巴细胞，能介导宿主对巨细胞病毒等病毒的早期防御。白介素15(IL-15)在病毒感染过程中上调，并驱动NK细胞的增殖。然而，IL-15对小鼠NK细胞分裂和死亡率的影响尚未得到定量研究。因此，我们开发了一系列两室(代表静止和分裂的NK细胞亚群)数学模型，结合了对调节NK细胞扩增的动力学参数的不同假设。使用实验得出的分裂和死亡率，我们通过将NK细胞数量的预测与独立的实验结果进行比较，检验了每个模型的假设，并证明了未分裂和分裂的NK细胞亚群的动力学参数是不同的。IL-15通过调节募集和分裂速率而不是死亡率来影响NK细胞的扩增。观察到的第一次分裂的时间延迟可以用未分裂和分裂的NK细胞亚群的动力学参数的差异来解释。尽管IL-15对第一次分裂的延迟时间没有显著影响，但随着IL-15浓度的升高，未分裂的NK细胞进入复制亚群的比例增加。我们的模型定量预测了当IL-15刺激减少时NK细胞聚集的变化，表明当细胞因子刺激被去除时，NK细胞分裂承诺被中断。总之，这一定量分析揭示了对NK细胞增殖的体外调控的新见解，并为体内NK细胞对病毒感染的反应建模提供了基础。
Natural killer (NK) cells are innate lymphocytes that mediate early host defense against viruses, such as cytomegalovirus. Interleukin 15 (IL-15) is upregulated during viral infections and drives the expansion of NK cells. However, the influence of IL-15 on murine NK cell division and death rates has not been quantitatively studied. Therefore, we developed a series of two-compartment (representing quiescent and dividing NK cell subpopulations) mathematical models, incorporating different assumptions about the kinetic parameters regulating NK cell expansion. Using experimentally derived division and death rates, we tested each model’s assumptions by comparing predictions of NK cell numbers with independent experimental results and demonstrated that the kinetic parameters are distinct for non-dividing and dividing NK cell subpopulations. IL-15 influenced NK cell expansion by modulating recruitment and division rates to a greater extent than death rates. The observed time delay to first division could be accounted for by differences in the kinetic parameters of non-dividing and dividing subsets of NK cells. Although the duration of the time delay to first division was not significantly influenced by IL-15, the recruitment of non-dividing NK cells into the replicating subpopulation increased with higher IL-15 concentrations. Our model quantitatively predicted changes in NK cell accumulation when IL-15 stimulation was reduced, demonstrating that NK cell divisional commitment was interrupted when cytokine stimulation was removed. In summary, this quantitative analysis reveals novel insights into the in vitro regulation of NK cell proliferation and provides a foundation for modeling in vivo NK cell responses to viral infections.
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影响因子：
6
作者：
Lima, M;Almeida, J;Orfao, A
通讯作者：
Orfao, A
影响因子：
30.5
作者：
Kaech, SM;Ahmed, R
通讯作者：
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DOI：
10.1084/jem.191.5.771
发表时间：
2000-03-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kennedy MK;Glaccum M;Brown SN;Butz EA;Viney JL;Embers M;Matsuki N;Charrier K;Sedger L;Willis CR;Brasel K;Morrissey PJ;Stocking K;Schuh JC;Joyce S;Peschon JJ
通讯作者：
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影响因子：
20.3
作者：
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通讯作者：
Caligiuri, MA
影响因子：
14.2
作者：
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通讯作者：
Yokoyama, Wayne M.