Development and activation of regulatory T cells in the human fetus
Development and activation of regulatory T cells in the human fetus
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DOI：
10.1002/eji.200425763
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Spits, H
中科院分区：
文献类型：
--
作者：
Cupedo, T;Nagasawa, M;Spits, H
关于成人免疫系统中调节性T细胞(Treg)的功能特性的了解越来越多，但关于这些细胞在人类胚胎发育过程中的生成和功能的数据很少。在这项研究中，我们发现在胎儿胸腺中，CD25、GITR、CTLA4和CD122在从CD27(-)到CD27(+)的过渡阶段启动了CD25、GITR、CTLA4和CD122的表达。此外，CD4(+)CD25(+)胎儿胸腺细胞已经具有抑制CD25(-)细胞增殖的潜力。在离开胸腺后，FoxP3(+)CD4(+)CD25(+)Treg进入胎儿淋巴结和脾，在那里它们获得了启动/记忆表型。提出了一种人胎儿Treg发育的模型，包括两个连续的成熟步骤：在胸腺中启动调节表型和抑制活性；以及随后在外周淋巴器官内激活。激活后，FoxP3+CD4+CD25+Treg通过自身反应淋巴细胞抑制潜在的有害反应，并维持发育中的胎儿体内的动态平衡。
There is an increasing amount of knowledge on the functional properties of regulatory T cells (Treg) in the adult immune system, but data on the generation and function of these cells during human embryonic development are scarce. In this study, we show that in the fetal thymus, double-positive cells initiate expression of CD25, GITR, CTLA4 and CD122 during their transition from the CD27(-) to the CD27(+) stage. Moreover, CD4(+)CD25(+) fetal thymocytes already have the potential to suppress proliferation of CD25(-) cells. After leaving the thymus, FoxP3(+)CD4(+)CD25(+) Treg enter the fetal lymph nodes and spleen, where they acquire a primed/memory phenotype. A model is proposed for the development of human fetal Treg that encompasses two sequential maturation steps: initiation of a regulatory phenotype and suppressive activity in the thymus; and subsequent activation within the peripheral lymphoid organs. Upon activation, FoxP3+CD4+CD25+ Treg suppress potentially deleterious responses by autoreactive lymphocytes and maintain homeostasis within the developing fetus.