Journal
IMMUNITY
Volume 28, Issue 1, Pages 100-111Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2007.11.021
Keywords
-
Categories
Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI061478] Funding Source: NIH RePORTER
- NIAID NIH HHS [R01 AI061478-03, R01 AI061478, R01 AI061478-04] Funding Source: Medline
Ask authors/readers for more resources
Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3(-)CD4(+)CD8(-) thymocytes. By using intrathymic transfer, we found that the CD25(hi) subset is highly enriched in Treg cell precursors. This was supported by tracking of thymocyte development via analysis of T cell receptor (TCR) repertoires in a TCR-beta transgenic model. These Treg cell precursors exist at a developmental stage where they are poised to express Foxp3 without further TCR engagement, requiring only stimulation by interleukin-2 (IL-2) or IL-15. Thus, we propose that the selection of self-reactive thymocytes into the Treg cell subset occurs via an instructive rather than stochastic-selective model whereby TCR signals result in the expression of proximal IL-2 signaling components facilitating cytokine-mediated induction of Foxp3.
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