TY - JOUR
T1 - Intraclonal competition limits the fate determination of regulatory T cells in the thymus
AU - Bautista, Jhoanne L.
AU - Lio, Chan Wang J.
AU - Lathrop, Stephanie K.
AU - Forbush, Katherine
AU - Liang, Yuqiong
AU - Luo, Jingqin
AU - Rudensky, Alexander Y.
AU - Hsieh, Chyi Song
N1 - Funding Information:
We thank N. Santacruz and J. Hunn for technical assistance, and K. Murphy, W. Yokoyama, P. Allen, W. Swat, J. Scott-Brown and J. Fontenot for discussions and critical review of the manuscript. Supported by the Arthritis Foundation, Burroughs Wellcome Fund and the US National Institutes of Health (C.-S.H.).
PY - 2009
Y1 - 2009
N2 - Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell-derived TCR. Unexpectedly, we found that efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (<1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other Treg cell-derived TCRs. Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection.
AB - Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell-derived TCR. Unexpectedly, we found that efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (<1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other Treg cell-derived TCRs. Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection.
UR - http://www.scopus.com/inward/record.url?scp=65749120321&partnerID=8YFLogxK
U2 - 10.1038/ni.1739
DO - 10.1038/ni.1739
M3 - Article
C2 - 19430476
AN - SCOPUS:65749120321
VL - 10
SP - 610
EP - 617
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 6
ER -