白细胞介素-2 在体外的基质细胞系上将不成熟的双阴性胸腺细胞诱导为表达 Foxp3 的 γδ T 细胞。

Interleukin-2 drives immature double negative thymocytes into γδ T cells expressing Foxp3 on a stromal cell line in vitro.

机构信息

Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.

出版信息

Biochem Biophys Res Commun. 2014 Oct 3;452(4):912-9. doi: 10.1016/j.bbrc.2014.08.155. Epub 2014 Sep 10.

DOI:10.1016/j.bbrc.2014.08.155

Abstract

γδ T cells are exported from the thymus as innate-like lymphocytes that can immediately respond to antigens. In the thymus, γδ T cells diverge into functionally distinct lineages. It is not known whether γδ T cells differentiate into regulatory cells that express Foxp3, which is an essential transcription factor for CD4(+) regulatory T cells. In this study, we analyzed CD25(+) immature thymocytes that give rise to both αβ and γδ thymocytes. These precursor cells have the potential to differentiate into Foxp3(+) γδ T cells on a stromal cell line, TSt4-Dll1. Development of Foxp3(+) γδ thymocytes in this culture was dependent on IL-2. IL-2 stimulation induced Id3, Egr1, and Egr3 expression in CD25(+) immature thymocytes, suggesting that it could activate signaling molecules that are downstream of TCR signaling. The induction of Foxp3 in precursor γδ T cells suggested that IL-2 could activate the Foxp3 gene early in thymocyte development.

摘要

γδ T 细胞作为先天样淋巴细胞从胸腺输出，可以立即对抗原做出反应。在胸腺中，γδ T 细胞分化为功能不同的谱系。目前尚不清楚 γδ T 细胞是否分化为表达 Foxp3 的调节细胞，Foxp3 是 CD4(+)调节性 T 细胞的必需转录因子。在这项研究中，我们分析了既能产生 αβ T 细胞又能产生 γδ T 细胞的 CD25(+)未成熟胸腺细胞。这些前体细胞在基质细胞系 TSt4-Dll1 上有可能分化为 Foxp3(+)γδ T 细胞。在这种培养物中，Foxp3(+)γδ 胸腺细胞的发育依赖于 IL-2。IL-2 刺激诱导 CD25(+)未成熟胸腺细胞中 Id3、Egr1 和 Egr3 的表达，表明它可以激活 TCR 信号下游的信号分子。前体 γδ T 细胞中 Foxp3 的诱导表明，IL-2 可以在胸腺细胞发育的早期激活 Foxp3 基因。