Fluorochrome‐based definition of naturally occurring Foxp3+ regulatory T cells of intra‐ and extrathymic origin

Fluorochrome‐based definition of naturally occurring Foxp3+ regulatory T cells of intra‐ and extrathymic origin
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基于荧光染料的胸腺内和胸腺外天然存在的 Foxp3+ 调节性 T 细胞的定义

DOI:
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发表时间:
2014
影响因子:
5.4
通讯作者:
Karsten Kretschmer
Karsten Kretschmer
中科院分区:
医学3区
文献类型:
--
作者:
C. Petzold;N. Steinbronn;M. Gereke;R. Strasser;T. Sparwasser;D. Bruder;R. Geffers;S. Schallenberg;Karsten Kretschmer

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在生理条件下,由于缺乏明确的标记来区分这些发育中的Treg细胞亚谱系的成熟后代,对自然诱导的胸腺内和胸腺外Foxp3+ Treg细胞的生物学研究一直受到阻碍。在这里,我们报告了双转基因小鼠的实验,其中红色荧光蛋白(RFP)在所有Foxp3+ Treg细胞中表达,而Foxp3依赖的GFP表达仅局限于胸腺内诱导的Foxp3+ Treg细胞。这种新颖的分子遗传工具使我们能够忠实地跟踪和表征自然诱导的胸腺内(RFP+GFP+)和胸腺外(RFP+GFP -)来源的Treg细胞。这些实验直接证明,胸腺外诱导的Treg细胞在很大程度上有助于稳定状态小鼠外周血淋巴组织中成熟的Foxp3+ Treg细胞。此外,我们提供的证据表明,胸腺内和胸腺外诱导的Foxp3+ Treg细胞具有不同的表型和功能亚谱系。
Under physiological conditions, studies on the biology of naturally induced Foxp3+ Treg cells of intra‐ and extrathymic origin have been hampered by the lack of unambiguous markers to discriminate the mature progeny of such developmental Treg‐cell sublineages. Here, we report on experiments in double‐transgenic mice, in which red fluorescent protein (RFP) is expressed in all Foxp3+ Treg cells, whereas Foxp3‐dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP−) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3+ Treg cells residing in peripheral lymphoid tissues of steady‐state mice. Furthermore, we provide evidence that intra‐ and extrathymically induced Foxp3+ Treg cells represent distinct phenotypic and functional sublineages.
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