The natural CD25+ FOXP3+ regulatory T cell (Treg) population is generated as a distinct lineage in the thymus, but the details of Treg development in humans remain unclear, and the timing of Treg commitment is also contested. Here we have analyzed the emergence of CD25+ cells at the CD4+CD8+ double positive (DP) stage in the human thymus. We show that these cells share T cell receptor repertoire with CD25+ CD4 single-positive thymocytes, believed to be committed Tregs. They already have a fully demethylated FOXP3 enhancer region and thus display stable expression of FOXP3 and the associated Treg phenotype. Transcriptome analysis also grouped the DP CD25+ and CD4 CD25+ thymocytes apart from the CD25- subsets. Together with earlier studies, our data are consistent with human Treg commitment already at the DP thymocyte stage. We suggest that the most important antigens and signals necessary for human Treg differentiation may be found in the thymic cortex.

中文翻译：

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表观遗传学和转录分析支持CD4 + CD8 +胸腺细胞阶段的人类调节性T细胞潜伏期。

天然CD25 + FOXP3 +调节性T细胞（Treg）群体是作为胸腺中的独特谱系生成的，但是人类中Treg发育的细节仍然不清楚，而且Treg承诺的时机也存在争议。在这里，我们分析了人胸腺CD4 + CD8 +双阳性（DP）阶段CD25 +细胞的出现。我们显示，这些细胞与CD25 + CD4单阳性胸腺细胞共享T细胞受体库，据信是Tregs。它们已经具有完全去甲基化的FOXP3增强子区域，因此显示FOXP3和相关的Treg表型的稳定表达。转录组分析也将DP CD25 +和CD4 CD25 +胸腺细胞分为CD25-亚组。连同较早的研究，我们的数据与DP胸腺细胞阶段人类Treg的投入一致。