Quantifying Thymic Export: Combining Models of Naive T Cell Proliferation and TCR Excision Circle Dynamics Gives an Explicit Measure of Thymic Output
Quantifying Thymic Export: Combining Models of Naive T Cell Proliferation and TCR Excision Circle Dynamics Gives an Explicit Measure of Thymic Output
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DOI：
10.4049/jimmunol.0900743
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发表时间：
2009-10-01
影响因子：
4.4
通讯作者：
Callard, Robin
中科院分区：
文献类型：
--
作者：
Bains, Iren;Thiebaut, Rodolphe;Callard, Robin
要了解T细胞的动态平衡，需要了解胸腺新T细胞的输出率，这一速度一直令人惊讶地难以估计。TCR切除环(TREC)含量已被用作胸腺输出的替代指标，但这一数量受细胞分裂和幼稚T细胞损失的影响，不是胸腺输出的直接衡量标准。在这项研究中，我们提出了一种通过结合两个简单的数学模型来量化人类胸腺输出的方法。一种使用Ki67数据来计算外周原始T细胞的生成率，而另一种则跟踪TREC的动态。将这些模型结合起来，可以将胸腺和细胞分裂对T细胞日产量的贡献分开。该方法是用已发表的关于Ki67表达和健康人初始CD4(+)T细胞内TRECs的数据来说明的。我们得到了从出生到20岁的胸腺输出与年龄的关系的定量估计。胸腺的T细胞输出率经历了三个不同的阶段：从出生到1岁时达到高峰，然后迅速退化，直到类似8岁，然后更缓慢地下降，直到20岁。我们的模型显示的退缩率与胸腺上皮间隙预测的胸腺功能的独立估计是一致的。我们的方法允许在个体的基础上非侵入性地估计胸腺的输出，并可能提供一种评估胸腺在HIV等疾病中的作用的方法。免疫学杂志，2009,183：4329-4336。
Understanding T cell homeostasis requires knowledge of the export rate of new T cells from the thymus, a rate that has been surprisingly difficult to estimate. TCR excision circle (TREC) content has been used as a proxy for thymic export, but this quantity is influenced by cell division and loss of naive T cells and is not a direct measure of thymic export. We present in this study a method for quantifying thymic export in humans by combining two simple mathematical models. One uses Ki67 data to calculate the rate of peripheral naive T cell production, whereas the other tracks the dynamics of TRECs. Combining these models allows the contributions of the thymus and cell division to the daily production rate of T cells to be disentangled. The method is illustrated with published data on Ki67 expression and TRECs within naive CD4(+) T cells in healthy individuals. We obtain a quantitative estimate for thymic export as a function of age from birth to 20 years. The export rate of T cells from the thymus follows three distinct phases, as follows: an increase from birth to a peak at 1 year, followed by rapid involution until similar to 8 years, and then a more gradual decline until 20 years. The rate of involution shown by our model is compatible with independent estimates of thymic function predicted by thymic epithelial space. Our method allows nonintrusive estimation of thymic output on an individual basis and may provide a means of assessing the role of the thymus in diseases such as HIV. The Journal of Immunology, 2009, 183: 4329-4336.