TY - JOUR
T1 - A Two-Step Process for Thymic Regulatory T Cell Development
AU - Lio, Chan Wang Joaquim
AU - Hsieh, Chyi Song
N1 - Funding Information:
We would like to thank N. Bogacki and P. Simmons for expert technical assistance; D. Pham for his crucial role in the analysis of TCR repertoires; S. Lathrop, J. Fontenot (Biogen Idec), J. Scott-Brown (U. of Colorado), W. Yokoyama, P. Allen, and J. Bautista for helpful discussions and critical review of the manuscript; and A. Rudensky for kindly providing the Foxp3 gfp reporter and TCli TCR-β transgenic mice. Supported by the Arthritis Foundation, Burroughs Wellcome Fund, and National Institutes of Health (C.-S.H.) and the Tertiary Education Services Office, Macau S.A.R. (C.-W.J.L.). The authors have no conflicts of interest to report.
PY - 2008/1/18
Y1 - 2008/1/18
N2 - 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 CD25hi 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-β 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.
AB - 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 CD25hi 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-β 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.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=37849009964&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2007.11.021
DO - 10.1016/j.immuni.2007.11.021
M3 - Article
C2 - 18199417
AN - SCOPUS:37849009964
SN - 1074-7613
VL - 28
SP - 100
EP - 111
JO - Immunity
JF - Immunity
IS - 1
ER -