A Mathematical Model of the Effects of Aging on Naive T Cell Populations and Diversity
A Mathematical Model of the Effects of Aging on Naive T Cell Populations and Diversity
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DOI：
10.1007/s11538-019-00630-z
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发表时间：
2019-07-01
影响因子：
3.5
通讯作者：
Chou, Tom
中科院分区：
文献类型：
--
作者：
Lewkiewicz, Stephanie;Chuang, Yao-li;Chou, Tom
已知人类适应性免疫应答在老年时减弱，导致病原体引起的疾病的严重程度增加，疫苗效力差，以及老年人癌症的患病率较高。与免疫相关的T细胞区室侵蚀已被认为是可能的原因，但驱动这种免疫衰老的潜在机制尚未被定量建模和系统分析。T细胞受体的多样性，或T细胞池的病原体衍生的抗原反应性的程度，是众所周知的，随着年龄的增长而减少，但固有的实验困难排除了准确的分析，在整个生物体水平。在本文中，我们制定了一个机械的数学模型的T细胞群体动态的免疫克隆亚群水平，提供了定量的多样性估计。我们定义了不同的多样性估计值，这取决于特定免疫克隆中细胞的个体数量。我们发现，随着年龄的增长，多样性下降，主要是由于减少胸腺输出的新的T细胞和由此产生的整体损失的小免疫克隆。
The human adaptive immune response is known to weaken in advanced age, resulting in increased severity of pathogen-born illness, poor vaccine efficacy, and a higher prevalence of cancer in the elderly. Age-related erosion of the T cell compartment has been implicated as a likely cause, but the underlying mechanisms driving this immunosenescence have not been quantitatively modeled and systematically analyzed. T cell receptor diversity, or the extent of pathogen-derived antigen responsiveness of the T cell pool, is known to diminish with age, but inherent experimental difficulties preclude accurate analysis on the full organismal level. In this paper, we formulate a mechanistic mathematical model of T cell population dynamics on the immunoclonal subpopulation level, which provides quantitative estimates of diversity. We define different estimates for diversity that depend on the individual number of cells in a specific immunoclone. We show that diversity decreases with age primarily due to diminished thymic output of new T cells and the resulting overall loss of small immunoclones.