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经FOXP3转导的Jurkat - T细胞作为调节性T(Treg)样细胞的功能和基因组分析。

Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells.

作者信息

Kim Joon-Young, Kim Han-Jong, Hurt Elaine M, Chen Xin, Howard O M Zack, Farrar William L

机构信息

Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA.

Cancer Stem Cell Section, Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-78, Frederick, MD 21702, USA.

出版信息

Biochem Biophys Res Commun. 2007 Oct 12;362(1):44-50. doi: 10.1016/j.bbrc.2007.07.187. Epub 2007 Aug 10.

Abstract

FOXP3, a forkhead transcription factor is essential for the development and function of CD4(+)CD25(+) regulatory T cells (Tregs). In contrast to conversion of murine naive T cells to Tregs by transduction of Foxp3, it is controversial whether ectopic expression of FOXP3 in human CD4(+) T cells is sufficient for acquisition of suppressive activity. Here, we show that retroviral transduction of FOXP3 induces a Treg phenotype in human leukemic CD4(+) Jurkat-T cells, evidenced by increased expression of Treg-associated cell surface markers as well as inhibition of cytokine production. Furthermore, FOXP3-transduced Jurkat-T cells suppress the proliferation of human CD4(+)CD25(-) T cells. Additionally, DNA microarray analysis identifies Treg-related genes regulated by FOXP3. Our study demonstrates that enforced expression of FOXP3 confers Treg-like properties on Jurkat-T cells, which can be a convenient and efficient Treg-like cell model for further study to identify Treg cell surface markers and target genes regulated by FOXP3.

摘要

FOXP3是一种叉头转录因子,对CD4(+)CD25(+)调节性T细胞(Tregs)的发育和功能至关重要。与通过转导Foxp3将小鼠幼稚T细胞转化为Tregs不同,FOXP3在人CD4(+) T细胞中的异位表达是否足以获得抑制活性仍存在争议。在此,我们表明,FOXP3的逆转录病毒转导可诱导人白血病CD4(+) Jurkat-T细胞出现Treg表型,这表现为Treg相关细胞表面标志物的表达增加以及细胞因子产生受到抑制。此外,FOXP3转导的Jurkat-T细胞可抑制人CD4(+)CD25(-) T细胞的增殖。此外,DNA微阵列分析确定了受FOXP3调控的Treg相关基因。我们的研究表明,FOXP3的强制表达赋予Jurkat-T细胞类似Treg的特性,这可以成为一种方便且高效的类似Treg细胞模型,用于进一步研究以鉴定Treg细胞表面标志物和受FOXP3调控的靶基因。

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