Three-cell interactions in T cell-mediated suppression?: A mathematical analysis of its quantitative implications
Three-cell interactions in T cell-mediated suppression?: A mathematical analysis of its quantitative implications
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DOI：
10.4049/jimmunol.166.9.5356
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Carneiro, J
中科院分区：
文献类型：
--
作者：
León, K;Peréz, R;Carneiro, J
为了进一步了解T细胞介导的抑制，我们研究了调节性T细胞抑制其他T细胞（靶细胞）的假设的合理性，而两种细胞都与一种APC结合。我们使用一个数学模型来分析在体外抑制试验中的增殖抑制评分。该模型是细胞培养现实的根本简化，假设胸苷掺入与靶细胞的数量成比例，所述靶细胞将与不含调节细胞的APC瞬时形成缀合物。根据该模型，抑制指数应该主要由每个APC的调节细胞的数量决定，并且应该对靶细胞的数量不敏感。我们重新分析了几个已发表的数据集，证实了这一预期。此外，我们证明，瞬时抑制指数有一个绝对的限制作为每个APC的调节细胞的数量的函数。通过计算这个极限，我们发现该模型可以解释两个非互斥条件下的数据。第一，仅约15%的用于抑制测定的APC与T细胞形成缀合物。其次，调节细胞群的生长取决于靶细胞，使得当与靶细胞共培养时，每个APC的调节细胞的数量增加并克服其限制。然而，如果这些可测试的条件都不满足，则可以得出结论，体外抑制不需要形成多细胞缀合物。
Aiming to further our understanding of T cell-mediated suppression, we investigate the plausibility of the hypothesis that regulatory T cells suppress other T cells (target cells), while both cells are conjugated with one APC. We use a mathematical model to analyze the proliferation inhibition scored during in vitro suppression assays. This model is a radical simplification of cell culture reality, assuming that thymidine incorporation is proportional to the number of target cells that would instantaneously form conjugates with APCs that are free of regulatory cells. According to this model the inhibition index should be mainly determined by the number of regulatory cells per APC and should be insensitive to the number of target cells. We reanalyzed several published data sets, confirming this expectation. Furthermore, we demonstrate that the instantaneous inhibition index has an absolute limit as a function of the number of regulatory cells per APC. By calculating this limit we find that the model can explain the data under two non-mutually exclusive conditions. First, only similar to 15 % of APCs used in the suppression assays form conjugates with T cells. Second, the growth of the regulatory cell population depends on the target cells, such that the number of regulatory cells per APC increases when they are cocultured with target cells and overcomes its limit. However, if neither of these testable conditions is fulfilled, then one could conclude that suppression in vitro does not require the formation of multicellular conjugates.