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• W3015945615 abstract "The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset." @default.
• W3015945615 created "2020-04-17" @default.
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• W3015945615 date "2020-04-08" @default.
• W3015945615 modified "2023-10-14" @default.
• W3015945615 title "The Rules of Human T Cell Fate in vivo" @default.
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• W3015945615 doi "https://doi.org/10.3389/fimmu.2020.00573" @default.
• W3015945615 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7156550" @default.
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