衰老对初始T细胞群体和多样性影响的数学模型
A mathematical model of the effects of aging on naive T-cell population and diversity
摘要：
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细胞区室的侵蚀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。已知T细胞受体多样性或T细胞池的病原体来源的抗原反应性的程度随着年龄的增长而减少，但固有的实验困难妨碍了在全生物体水平上的准确分析。在本文中，我们制定了一个机械数学模型的T细胞种群动力学的免疫克隆亚群水平上，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。
英文摘要：
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.
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