Leung Monica W L, Shen Shiqian, Lafaille Juan J
Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
J Exp Med. 2009 Sep 28;206(10):2121-30. doi: 10.1084/jem.20091033. Epub 2009 Sep 8.
Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3(+) regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3(+) lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3(+) cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3(+) cells was very low. However, intrathymic injection and bone marrow chimera experiments showed a saturable increase of the Foxp3(+) population when T reg TCR Tg cells were present in low numbers. Furthermore, when analyzing whole thymi of T reg TCR Tg RAG-deficient mice, we found significantly more Foxp3(+) cells than in conventional T cell TCR Tg mice. Our results indicate that although the TCR has an instructive role in determining Foxp3 expression, selection of Foxp3(+) individual clones in the thymus is limited by a very small niche.
众多研究强调了T细胞受体（TCR）与其配体之间的高亲和力相互作用在Foxp3（+）调节性T细胞（Treg细胞）选择过程中的重要性。为了确定TCR在引导T细胞分化为Foxp3（+）谱系中的作用，我们构建了表达来自Foxp3（+）细胞的TCR的转基因（Tg）小鼠。对与RAG缺陷小鼠杂交的TCR Tg小鼠的初步分析表明，Foxp3（+）细胞的百分比非常低。然而，胸腺内注射和骨髓嵌合体实验表明，当Treg TCR Tg细胞数量较少时，Foxp3（+）群体有可饱和的增加。此外，在分析Treg TCR Tg RAG缺陷小鼠的整个胸腺时，我们发现Foxp3（+）细胞比传统T细胞TCR Tg小鼠中的显著更多。我们的结果表明，尽管TCR在决定Foxp3表达方面具有指导作用，但胸腺中Foxp3（+）单个克隆的选择受到非常小的生态位的限制。
