Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento 6, 00161, Rome, Italy.
Ann Hematol. 2012 Feb;91(2):155-61. doi: 10.1007/s00277-011-1288-y. Epub 2011 Jul 6.
The aim of the study was to analyze and compare the functional properties and the gene expression profile of regulatory T cells (Tregs) isolated from cord blood (CB) units (n = 23) and from the peripheral blood (PB) of adult normal donors (n = 13). Tregs were purified from mononuclear cells and expanded for 6 days with anti-CD3, anti-CD28, and IL-2. CB and PB Tregs presented similar immunophenotypic features. However, Tregs isolated from CB presented a much higher expansion capacity; this was confirmed by the genomic characterization that showed in CB-derived Tregs significant enrichments of genes involved in cell proliferation, chromatin modification, and regulation of gene expression. All samples were positive for the FoxP3 gene and protein after expansion. CB and PB expanded Tregs exerted a comparable and potent suppressive function on the proliferative reaction of autologous T cells stimulated by allogeneic dendritic cells and presented a high in vitro IL-10 production capacity. Gene profile analysis also revealed for PB Tregs significant enrichments of genes involved in the adaptive immune response. These data offer further insights into the understanding of the biology of CB transplantation indicating a possible role played by CB Tregs in the suppression of the allogeneic T cell response.
本研究旨在分析和比较从脐带血(CB)(n=23)和成人正常供体外周血(PB)(n=13)分离的调节性 T 细胞(Tregs)的功能特性和基因表达谱。Tregs 从单核细胞中分离出来,并在抗 CD3、抗 CD28 和 IL-2 的作用下扩增 6 天。CB 和 PB Tregs 具有相似的免疫表型特征。然而,从 CB 分离的 Tregs 具有更高的扩增能力;这通过基因组特征得到了证实,该特征显示 CB 衍生的 Tregs 中与细胞增殖、染色质修饰和基因表达调控相关的基因显著富集。扩增后,所有样本的 FoxP3 基因和蛋白均呈阳性。CB 和 PB 扩增的 Tregs 对同种异体树突状细胞刺激的自体 T 细胞的增殖反应具有相似且强大的抑制作用,并且具有高体外 IL-10 产生能力。基因谱分析还显示 PB Tregs 中与适应性免疫反应相关的基因显著富集。这些数据为理解 CB 移植的生物学提供了进一步的见解,表明 CB Tregs 在抑制同种异体 T 细胞反应中可能发挥作用。