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

Vrisekoop, Nienke, den Braber, Ineke, de Boer, Anne Bregje, Ruiter, An F.C., Ackermans, Mariëtte T., van der Crabben, Saskia N., Schrijver, Elise H.R., Spierenburg, Gerrit, Sauerwein, Hans P., Hazenberg, Mette D., de Boer, Rob J., Miedema, Frank, Borghans, José A.M., Tesselaar, Kiki
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.16 pp. 6115-6120
CD4-positive T-lymphocytes, CD8-positive T-lymphocytes, adults, deuterium oxide, human population, humans, longevity, mathematical models, mice
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 ²H₂O labeling in young mice showed high thymic-dependent daily naïve T cell production, long term up- and down-labeling with ²H₂O 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.