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

Jhoanne L. Bautista, Chan Wang J. Lio, Stephanie K. Lathrop, Katherine Forbush, Yuqiong Liang, Jingqin Luo, Alexander Y. Rudensky, Chyi Song Hsieh

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180 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)610-617
Number of pages8
JournalNature immunology
Volume10
Issue number6
DOIs
StatePublished - May 11 2009

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    Bautista, J. L., Lio, C. W. J., Lathrop, S. K., Forbush, K., Liang, Y., Luo, J., Rudensky, A. Y., & Hsieh, C. S. (2009). Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nature immunology, 10(6), 610-617. https://doi.org/10.1038/ni.1739