Biology, Emory University, Atlanta, GA.
Immunology. 2014 Jun;142(2):167-75. doi: 10.1111/imm.12244.
The adaptive immune system requires a diverse T-cell repertoire to be able to respond to a wide variety of pathogens. Worryingly, the repertoire diversity declines dramatically in old age. As thymic output generates novel T cells, the conventional view holds that a decrease in this output with age is responsible for the loss in the repertoire. However, many additional factors affect the repertoire such as homeostatic turnover and antigen-dependent expansion in response to infection. Mathematical models taking a population biology perspective are important tools for understanding how the interplay between these factors affects the immune repertoire. These models suggest that thymic decline is not a major factor but rather that some combination of virus-induced proliferation and T-cell-intrinsic genetic or epigenetic changes gives rise to the oligoclonal expansions that cause the decline in T-cell diversity. We also discuss consequences for strategies to rejuvenate the immune repertoire in old age.
适应性免疫系统需要多样化的 T 细胞 repertoire 才能对各种病原体做出反应。令人担忧的是，老年时 repertoire 多样性会急剧下降。由于胸腺输出产生新的 T 细胞，因此传统观点认为，随着年龄的增长，这种输出的减少是 repertoire 丧失的原因。然而，许多其他因素会影响 repertoire，例如针对感染的体内平衡性更新和抗原依赖性扩增。从群体生物学角度考虑的数学模型是理解这些因素之间的相互作用如何影响免疫 repertoire 的重要工具。这些模型表明，胸腺下降并不是主要因素，而是病毒诱导的增殖和 T 细胞内在的遗传或表观遗传变化的某种组合导致了导致 T 细胞多样性下降的寡克隆扩增。我们还讨论了针对老年时使免疫 repertoire 年轻化的策略的后果。
