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

doi:10.1073/pnas.0709713105

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

*Department of Immunology, University Medical Center Utrecht, 3508 AB, Utrecht, The Netherlands;
^†Department of Clinical Viro-Immunology, Sanquin Research Center, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1000 GG, Amsterdam, The Netherlands;
Departments of ^‡Clinical Chemistry and
^§Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1100 DD, Amsterdam, The Netherlands; and
^¶Department of Theoretical Biology, Utrecht University, 3584 CH, Utrecht, The Netherlands

Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, and approved February 28, 2008 (received for review October 12, 2007)

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 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.

Footnotes

^‖To whom correspondence should be addressed at:
Department of Immunology, University Medical Center Utrecht, Lundlaan 6, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands.
E-mail: k.tesselaar{at}umcutrecht.nl
Author contributions: N.V., and I.d.B. contributed equally to this work; N.V., I.d.B., H.P.S., R.J.d.B., F.M., J.A.M.B., and K.T. designed research; N.V., I.d.B., A.B.d.B., A.F.C.R., M.T.A., S.N.v.d.C., E.H.R.S., G.S., and M.D.H. performed research; N.V., I.d.B., M.T.A., R.J.d.B., and J.A.M.B. analyzed data; and N.V., I.d.B., R.J.d.B., F.M., J.A.M.B., and K.T. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709713105/DCSupplemental.