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. 2008 Apr 22;105(16):6115-20.
doi: 10.1073/pnas.0709713105. Epub 2008 Apr 17.

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

Nienke Vrisekoop  1 , Ineke den Braber, Anne Bregje de Boer, An F C Ruiter, Mariëtte T Ackermans, Saskia N van der Crabben, Elise H R Schrijver, Gerrit Spierenburg, Hans P Sauerwein, Mette D Hazenberg, Rob J de Boer, Frank Miedema, José A M Borghans, Kiki Tesselaar
Affiliations

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

Nienke Vrisekoop et al. Proc Natl Acad Sci U S A. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
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.
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.
See this image and copyright information in PMC

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