Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter
Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter
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DOI：
10.1073/pnas.0501701102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Wan, YSY;Flavell, RA
调节性 T 细胞对于维持自我耐受和负面调节免疫反应至关重要。 Foxp3 是一种调节性 T 细胞特异性转录因子，作为调节性 T 细胞发育和功能的主调节因子。在这里，我们报告了小鼠模型的产生，其中表达红色荧光蛋白的双顺反子报告基因已被敲入内源性 Foxp3 基因座。使用该小鼠模型，我们评估了不同淋巴细胞区室中的 Foxp3 表达，并鉴定了以前未报告的 Foxp3 表达细胞。此外，我们还发现，体外活化的 CD4 T 细胞中 TGF-β 可以诱导 Foxp3 表达以及抑制功能。最后，我们证明不表达 Foxp3 的 CD4T 细胞在过继转移到免疫缺陷宿主后不能转化为表达 Foxp3 的细胞。这种Foxp3双顺反子报告基因敲入小鼠模型将大大加强对表达Foxp3的调节性T细胞的调节和功能的研究。
Regulatory T cells are critical for maintaining self-tolerance and to negatively regulate immune responses. Foxp3 is a regulatory T cell-specific transcription factor that functions as the master regulator of the development and function of regulatory T cells. Here, we report the generation of a mouse model, in which a bicistronic reporter expressing a red fluorescent protein has been knocked into the endogenous Foxp3 locus. Using this mouse model, we assessed Foxp3 expression in various lymphocyte compartments and identified previously unreported Foxp3-expressing cells. In addition, we showed that de novo Foxp3 expression along with suppressive function were induced by TGF-beta in activated CD4 T cells in vitro. Finally, we demonstrated that non-Foxp3-expressing CD4T cells could not be converted into Foxp3-expressing cells upon adoptive transfer into immunodeficient hosts. This Foxp3 bicistronic reporter knockin mouse model should greatly enhance the study of regulation and function of Foxp3-expressing regulatory T cells.