Towards a unified model of naive T cell dynamics across the lifespan.
Towards a unified model of naive T cell dynamics across the lifespan.
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DOI：
10.7554/elife.78168
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发表时间：
2022-06-09
期刊：
影响因子：
7.7
通讯作者：
Yates, Andrew J.
中科院分区：
文献类型：
--
作者：
Rane, Sanket;Hogan, Thea;Lee, Edward;Seddon, Benedict;Yates, Andrew J.
原始的CD4和CD8T细胞是适应性免疫的基石，但人们对它们在生命早期建立的动力学以及它们在胸腺释放后随着成熟而发生的动力学变化知之甚少。此外，由于原始T细胞存活所涉及的不同信号，长期以来一直有一个概念上有吸引力的观点，即随着胸腺活动的减弱，它们是由主动的体内平衡控制维持的。在这里，我们使用多种建模和实验方法来确定小鼠体内幼稚的CD4和CD8T细胞种群动态的统一模型，跨越它们的寿命。我们推断，这两个亚群很少分裂，并随着细胞年龄的增长而逐渐增加其生存能力。令人惊讶的是，这个简单的模型能够描述一生中幼稚的CD4T细胞动力学。相反，我们发现新产生的幼稚CD8T细胞在生命的前3-4周内丢失得更快，可能是由于记忆中的招募增加所致。我们没有发现新生儿分裂比率升高的证据，也没有证据表明任何年龄的幼稚T细胞数量都有反馈调节。我们展示了如何用不同的数据集来对抗数学模型，以揭示小鼠从出生到老年的幼稚T细胞动力学的定量和非常简单的图景。
Naive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics of their establishment early in life and how their kinetics change as they mature following release from the thymus are poorly understood. Further, due to the diverse signals implicated in naive T cell survival, it has been a long-held and conceptually attractive view that they are sustained by active homeostatic control as thymic activity wanes. Here we use multiple modelling and experimental approaches to identify a unified model of naive CD4 and CD8 T cell population dynamics in mice, across their lifespan. We infer that both subsets divide rarely, and progressively increase their survival capacity with cell age. Strikingly, this simple model is able to describe naive CD4 T cell dynamics throughout life. In contrast, we find that newly generated naive CD8 T cells are lost more rapidly during the first 3–4 weeks of life, likely due to increased recruitment into memory. We find no evidence for elevated division rates in neonates, or for feedback regulation of naive T cell numbers at any age. We show how confronting mathematical models with diverse datasets can reveal a quantitative and remarkably simple picture of naive T cell dynamics in mice from birth into old age.
影响因子：
3.7
作者：
Dong J;Chen Y;Xu X;Jin R;Teng F;Yan F;Tang H;Li P;Sun X;Li Y;Wu H;Zhang Y;Ge Q
通讯作者：
Ge Q