Intraclonal competition limits the fate determination  of regulatory T cells in the thymus.
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 (o1%) 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.
Bautista
Jhoanne L
JL
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
Lio
Chan-Wang J
CW
Lathrop
Stephanie K
SK
Forbush
Katherine
K
Liang
Yuqiong
Y
Luo
Jingqin
J
Rudensky
Alexander Y
AY
Hsieh
Chyi-Song
CS
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D002678:Chimera / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell