DiPaolo Richard J, Shevach Ethan M
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
Eur J Immunol. 2009 Jan;39(1):234-40. doi: 10.1002/eji.200838772.
CD4(+)Foxp3(+) Treg maintain peripheral tolerance and influence immune responses to foreign antigens. The thymus is an important source of Treg, but controversy exists as to whether T cells are selected into the Treg lineage based on signals received through TCR specific for self-peptides. To examine the specificity of TCR expressed by Treg and its effect on CD4(+) T-cell development, we generated Treg-TCR transgenic mice. Deletion of >90% of CD4(+) T cells in RAG-sufficient mice, and nearly 100% deletion in RAG(-/-) mice expressing this TCR indicate that the TCR is specific for an unknown, naturally expressed peptide in the thymus. Deletion occurs late in development, suggesting this peptide is presented by APC in the thymic medulla. These studies are the first to describe the effects of expressing a Treg-TCR on CD4(+) T-cell development. The implications of our data for models of Treg selection are discussed.
CD4(+)Foxp3(+)调节性T细胞维持外周免疫耐受并影响对外源抗原的免疫反应。胸腺是调节性T细胞的重要来源，但对于T细胞是否基于通过针对自身肽段的TCR所接收的信号而被选择进入调节性T细胞谱系存在争议。为了研究调节性T细胞表达的TCR的特异性及其对CD4(+) T细胞发育的影响，我们构建了调节性T细胞-TCR转基因小鼠。在RAG充足的小鼠中，>90%的CD4(+) T细胞缺失，而在表达该TCR的RAG(-/-)小鼠中，几乎100%的CD4(+) T细胞缺失，这表明该TCR对胸腺中一种未知的天然表达肽段具有特异性。缺失发生在发育后期，提示该肽段由胸腺髓质中的抗原呈递细胞呈递。这些研究首次描述了表达调节性T细胞-TCR对CD4(+) T细胞发育的影响。我们讨论了这些数据对调节性T细胞选择模型的意义。
