Intraclonal competition limits the fate determination of regulatory T cells in the thymus

被引：202

作者：

Bautista, Jhoanne L. ^{[1
]}

Lio, Chan-Wang J. ^{[1
]}

Lathrop, Stephanie K. ^{[1
]}

Forbush, Katherine ^{[2
,3
]}

Liang, Yuqiong ^{[2
,3
]}

Luo, Jingqin ^{[4
]}

Rudensky, Alexander Y. ^{[2
,3
]}

Hsieh, Chyi-Song ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA

[2] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[3] Univ Washington, Dept Immunol, Seattle, WA 98195 USA

[4] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 06期

基金：

美国国家卫生研究院;

关键词：

RECEPTOR TRANSGENIC MICE; HOMEOSTATIC PROLIFERATION; POSITIVE SELECTION; IN-VIVO; SELF; ANTIGEN; AUTOIMMUNITY; FOXP3; EXPRESSION; NAIVE;

D O I：

10.1038/ni.1739

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3(+)CD4(+) regulatory T cells (T(reg) cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic T(reg) cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring T(reg) cell-derived TCR. Unexpectedly, we found that efficient thymic T(reg) cell development occurred only when the antigen-specific T(reg) 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 T(reg) cell-derived TCRs. Our data demonstrate that thymic T(reg) 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.

引用

页码：610 / U74

页数：9

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