Discriminating between models of heterogeneous turnover by simulating the adoptive transfer experiments reported in ref. [14].

<p>(A) Observed and predicted kinetics of loss of naive CD4 cells taken from young (2 mo) (solid circles and solid lines) and aged (24 mo) (open circles and dashed lines) donors, using the adaptation (blue line), incumbent (red lines), and selection (green lines) models. Data were taken from Fig 2C in ref. [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003949#pbio.2003949.ref014" target="_blank">14</a>]. Parameters were taken from the fits to the data from WT and Tx mice reported in ref. [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003949#pbio.2003949.ref008" target="_blank">8</a>] and from our busulfan chimera data (left and right panels, respectively). (B) Predicting the trend in the loss of donor cells from the naive CD4 pool over 15 d, using AND TCR transgenic naive T cells taken from donors of four different ages (left panel, data reproduced from Fig. 4E in ref. [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003949#pbio.2003949.ref014" target="_blank">14</a>]). The three panels to the right show the models’ predicted fold loss of polyclonal naive CD4 and CD8 T cells 15 d after adoptive transfer, from donors of the same ages used in the AND adoptive transfer experiment. Due to intrinsic differences in the survival rates of AND and polyclonal naive cells, the absolute levels of recovery differ substantially, but the predicted trends show that only the adaptation model is able to reproduce a consistent increase in recovery with donor age. As in panel A, these predictions were generated using model parameters obtained from fits to the data from the busulfan chimeras (solid circles) and from ref. [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003949#pbio.2003949.ref008" target="_blank">8</a>] (open circles). Data are provided in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003949#pbio.2003949.s004" target="_blank">S3 Data</a>. TCR, T-cell receptor; Tx, thymectomised; WT, wild-type.