Department of Mathematics, UCLA, Los Angeles, CA, 90095-1555, USA.
Department of Mathematics, CalState-Northridge, Northridge, CA, 91330-8313, USA.
Bull Math Biol. 2019 Jul;81(7):2783-2817. doi: 10.1007/s11538-019-00630-z. Epub 2019 Jun 14.
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.
人体适应性免疫反应随着年龄的增长而减弱，导致病原体引起的疾病严重程度增加、疫苗效果不佳以及老年人癌症患病率上升。T 细胞群的衰老与年龄相关，这被认为是一个可能的原因，但导致这种免疫衰老的潜在机制尚未进行定量建模和系统分析。T 细胞受体多样性，即 T 细胞库对病原体衍生抗原的反应程度，随着年龄的增长而减少，但内在的实验困难排除了在全生物体水平上进行准确分析。在本文中，我们在免疫克隆亚群水平上构建了一个 T 细胞群体动力学的机制数学模型，该模型提供了多样性的定量估计。我们定义了不同的多样性估计值，这些估计值取决于特定免疫克隆中细胞的个体数量。我们表明，多样性随年龄的增长而减少，主要是由于新 T 细胞的胸腺输出减少以及由此导致的小免疫克隆的总体损失。
