TY - JOUR
T1 - Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool
AU - Vrisekoop, Nienke
AU - den Braber, Ineke
AU - de Boer, Anne Bregje
AU - Ruiter, An F C
AU - Ackermans, Mariëtte T
AU - van der Crabben, Saskia N
AU - Schrijver, Elise H R
AU - Spierenburg, Gerrit
AU - Sauerwein, Hans P
AU - Hazenberg, Mette D
AU - de Boer, Rob J
AU - Miedema, Frank
AU - Borghans, José A M
AU - Tesselaar, Kiki
PY - 2008/4/22
Y1 - 2008/4/22
N2 - 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.
AB - 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.
KW - Adult
KW - Animals
KW - Body Water/chemistry
KW - CD4-Positive T-Lymphocytes/immunology
KW - CD8-Positive T-Lymphocytes/immunology
KW - Cell Movement/immunology
KW - Deuterium Oxide/analysis
KW - Granulocytes/immunology
KW - Half-Life
KW - Humans
KW - Isotope Labeling
KW - Mice
KW - Mice, Inbred C57BL
KW - Models, Immunological
KW - Thymus Gland/immunology
U2 - https://doi.org/10.1073/pnas.0709713105
DO - https://doi.org/10.1073/pnas.0709713105
M3 - Article
C2 - 18420820
SN - 0027-8424
VL - 105
SP - 6115
EP - 6120
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 16
ER -