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

JL Bautista, CWJ Lio, SK Lathrop, K Forbush… - Nature …, 2009 - nature.com
JL Bautista, CWJ Lio, SK Lathrop, K Forbush, Y Liang, J Luo, AY Rudensky, CS Hsieh
Nature immunology, 2009nature.com
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 …
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.
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