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

In mice, recent thymic emigrants (RTEs) make up a large part of the naive 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 (H2O)-H-2 labeling in young mice showed high thymic-dependent daily naive T cell production, long term up and down-labeling with 211120 in human adults revealed a low daily production of naive T cells. Using mathematical modeling, we estimated human naive 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 naive 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 naive T cells that are newly produced are preferentially incorporated in the peripheral pool.