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.
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
Jhoanne L
JL
Bautista
Chan-Wang J
CW
Lio
Stephanie K
SK
Lathrop
Katherine
K
Forbush
Yuqiong
Y
Liang
Jingqin
J
Luo
Alexander Y
AY
Rudensky
Chyi-Song
CS
Hsieh
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