Three-cellinteractions in T cell-mediated suppression? A mathematical analysis of its quantitative implications

摘要

Aiming to further our understanding of T cell-mediated suppression, we investigate the plausibility of the hypothesis that reg latory T cells suppress other T cells (target cells), while both cells are conjugated with one APC. We use a mathematical moc to analyze the proliferation inhibition scored during in vitro suppression assays. This model is a radical simplification of c culture reality, assuming that thymidine incorporation is proportional to the number of target cells that would instantaneotu form conjugates with APCs that are free of regulatory cells. According to this model the inhibition index should be main determined by the number of regulatory cells per APC and should be insensitive to the number of target cells. We reanalyzi several published data sets, confirming this expectation. Furthermore, we demonstrate that the instantaneous inhibition index h an absolute limit as a function of the number of regulatory cells per APC. By calculating this limit we find that the model ci explain the data under two non-mutually exclusive conditions. First, only 15% of APCs used in the suppression assays for conjugates with T cells. Second, the growth of the regulatory cell population depends on the target cells, such that the number regulatory cells per APC increases when they are cocultured with target cells and overcomes its limit. However, if neither of the testable conditions is fulfilled, then one could conclude that suppression in vitro does not require the formation of multicellul conjugates.