arXiv 1802.050942018-02-14q-bio.CBq-bio.QM

用人体数据校准的CD8 + T细胞应答的数学研究

A mathematical study of CD8+ T cell responses calibrated with human data

John Paul Gosling, Sheeja M. Krishnan, Grant Lythe, Benny Chain, Cameron MacKay, Carmen Molina-París

摘要：

对人类免疫CD8 + T细胞应答过程中发生的增殖和分化的调节机制仍然缺乏完整的理解。人类临床数据通常限于血细胞计数，但这些反应的起始发生在引流淋巴结中;淋巴结中产生的抗原特异性效应和记忆CD8 + T细胞迁移到需要它们的组织中。我们使用近似贝叶斯计算与确定性数学模型的CD8 + T细胞群体（幼稚，中央记忆，效应记忆和效应）和黄热病病毒疫苗的数据，以推断这些CD8 + T细胞群体在三个空间区室的动态：引流淋巴结，循环和皮肤。我们利用文献获得了人CD8 + T细胞群亚群的分裂和死亡率以及胸腺输出率。在免疫应答过程中分化潜力降低的假设下，我们发现，随着驱动免疫应答的T细胞克隆型数量的增加，从初始CD8 + T细胞分化为效应CD8 + T细胞所需的分裂数量减少，支持在小鼠研究中观察到的"劳动分工"假设。我们还考虑了反向分化的情况，增加潜在的假设。黄热病毒疫苗接种数据更好地支持了下降势模型。

英文摘要：

Complete understanding of the mechanisms regulating the proliferation and differentiation that takes place during human immune CD8+ T cell responses is still lacking. Human clinical data is usually limited to blood cell counts, yet the initiation of these responses occurs in the draining lymph nodes; antigen-specific effector and memory CD8+ T cells generated in the lymph nodes migrate to those tissues where they are required. We use approximate Bayesian computation with deterministic mathematical models of CD8+ T cell populations (naive, central memory, effector memory and effector) and yellow fever virus vaccine data to infer the dynamics of these CD8+ T cell populations in three spatial compartments: draining lymph nodes, circulation and skin. We have made use of the literature to obtain rates of division and death for human CD8+ T cell population subsets and thymic export rates. Under the decreasing potential hypothesis for differentiation during an immune response, we find that, as the number of T cell clonotypes driven to an immune response increases, there is a reduction in the number of divisions required to differentiate from a naive to an effector CD8+ T cell, supporting the "division of labour" hypothesis observed in murine studies. We have also considered the reverse differentiation scenario, the increasing potential hypothesis. The decreasing potential model is better supported by the yellow fever virus vaccine data.

机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。

摘要：

英文摘要：

相关论文