Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 212, Issue 10, Pages 1589-1601Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20142143
Keywords
-
Categories
Funding
- German Research Foundation (DFG
- Emmy-Noether Program) [KR2320/2-1, SFB738-A7, KR2320/3-1, EXC62]
- Braukmann-Wittenberg- Herz-Stiftung
Ask authors/readers for more resources
Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that similar to 160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available