Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool

Abstract

In mice, recent thymic emigrants (RTEs) make up a large part of the naïve T cell pool and have been suggested to be a distinct short-lived pool. In humans, however, the life span and number of RTEs are unknown. Although (2)H(2)O labeling in young mice showed high thymic-dependent daily naïve T cell production, long term up- and down-labeling with (2)H(2)O in human adults revealed a low daily production of naïve T cells. Using mathematical modeling, we estimated human naïve CD4 and CD8 T cell half-lives of 4.2 and 6.5 years, respectively, whereas memory CD4 and CD8 T cells had half-lives of 0.4 and 0.7 year. The estimated half-life of recently produced naïve T cells was much longer than these average half-lives. Thus, our data are incompatible with a substantial short-lived RTE population in human adults and suggest that the few naïve T cells that are newly produced are preferentially incorporated in the peripheral pool.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Thymic output is important for the maintenance of the naïve T cell pool in young mice and can be quantitated by using 2H2O labeling. (A and B) Absolute numbers of total (A) and naïve (B) CD4 and CD8 T cells in spleen of three control (black bars) and four thymectomized (open bars) animals 14–16 weeks after time of surgery. (C) Accumulated 2H2O-labeling in naïve CD4 and CD8 T cells of the same euthymic and athymic mice after a 9- to 10-week labeling period. Data are displayed as mean ± standard error of the mean (n = 3–4). *, P ≤ 0.05 is considered significant. (D) Percentage of Ki67+ cells within the naïve CD4 and naïve CD8 T cell pool of control (●) and thymectomized (+) mice at different time points before and after thymectomy.

Fig. 2.

Best fits of the naïve and memory CD4 and CD8 T cell enrichment curves. Label enrichment was scaled between 0 and 100% by normalizing for the percentage label obtained in granulocytes (see SI Text). In the graph, the end of the labeling period is marked by a vertical line.