Department of Oncology, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2012;7(3):e34547. doi: 10.1371/journal.pone.0034547. Epub 2012 Mar 30.
Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios(+) and Helios(-) Treg, we profiled cell-surface markers of FoxP3(+) Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios(+) Treg and that a Helios(+) Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios(+) Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios(+) Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios(+) Treg proliferated more than Helios(-) Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios(+) cells in culture. Taken together, these data show that Helios(+) Treg represent a functional subset with associated CD103 and GITR expression.
Helios 是一个 Ikaros 家族转录因子，在调节性 T 细胞（Treg）中优先在 mRNA 和蛋白水平表达。Helios 的表达之前似乎仅限于胸腺来源的 Treg。与最近的数据一致，我们在这里显示 Helios 的表达在某些条件下可以在体外诱导。为了了解 Helios(+)和 Helios(-)Treg 之间的表型和功能差异，我们使用未经处理的脾细胞对 FoxP3(+)Treg 的细胞表面标志物进行了分析。我们发现 CD103 和 GITR 在 Helios(+)Treg 的一部分上高表达，并且可以通过使用这两个标志物的 FACS 分选显著富集 Helios(+)Treg 群体。实时定量 PCR (qPCR) 分析显示 Helios(+)Treg 中 TGF-β 消息增加，这与该群体可能具有增强的调节潜能一致。在荷瘤小鼠中，我们发现 Helios(+)Treg 在肿瘤组织中相对过表达，BrdU 研究表明，在体内，Helios(+)Treg 的增殖速度比 Helios(-)Treg 快。我们假设富含 Helios 的 Treg 可能发挥更强的抑制作用。通过体外抑制实验，我们表明 Treg 功能与培养物中 Helios(+)细胞的绝对数量相关。综上所述，这些数据表明 Helios(+)Treg 代表具有相关 CD103 和 GITR 表达的功能亚群。
