Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Eur J Immunol. 2014 Sep;44(9):2712-20. doi: 10.1002/eji.201444529. Epub 2014 Jul 1.
Natural Treg cells acquire their lineage-determining transcription factor Foxp3 during development in the thymus and are important in maintaining immunologic tolerance. Here, we analyzed the composition of the thymic Treg-cell pool using RAG2-GFP/FoxP3-RFP dual reporter mice and found that a population of long-lived GFP(-) Treg cells exists in the thymus. These long-lived Treg cells substantially increased with age, to a point where they represent >90% of the total thymic Treg-cell pool at 6 months of age. In contrast, long-lived conventional T cells remained at ∼ 15% of the total thymic pool at 6 months of age. Consistent with these studies, we noticed that host-derived Treg cells represented a large fraction (∼ 10%) of the total thymic Treg-cell pool in bone marrow chimeras, suggesting that long-lived Treg cells also reside in the thymus of these mice. The pool of long-lived Treg cells in the thymus was sustained by retention of Treg cells in the thymus and by recirculation of peripheral Treg cells back into the thymus. These long-lived thymic Treg cells suppressed T-cell proliferation to an equivalent extent to splenic Treg cells. Together, these data demonstrate that long-lived Treg cells accumulate in the thymus by both retention and recirculation.
天然调节性 T 细胞（Treg 细胞）在胸腺中发育过程中获得其谱系决定转录因子 Foxp3，并在维持免疫耐受中发挥重要作用。在这里，我们使用 RAG2-GFP/FoxP3-RFP 双报告小鼠分析了胸腺 Treg 细胞池的组成，发现胸腺中存在一群长寿的 GFP(-) Treg 细胞。这些长寿 Treg 细胞随年龄显著增加，在 6 个月大时，它们占胸腺 Treg 细胞池的>90%。相比之下，长寿常规 T 细胞在 6 个月大时仍保持在总胸腺池的约 15%。与这些研究一致，我们注意到，在骨髓嵌合体中，宿主来源的 Treg 细胞占胸腺 Treg 细胞池的很大一部分（约 10%），这表明长寿 Treg 细胞也存在于这些小鼠的胸腺中。胸腺中长寿 Treg 细胞池的维持是通过 Treg 细胞在胸腺中的保留和外周 Treg 细胞再循环回胸腺来实现的。这些长寿的胸腺 Treg 细胞对 T 细胞增殖的抑制作用与脾脏 Treg 细胞相当。总之，这些数据表明，长寿 Treg 细胞通过保留和再循环在胸腺中积累。
