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脐带血单核细胞来源树突状细胞的功能异质性。

Functional Heterogeneity of Umbilical Cord Blood Monocyte-Derived Dendritic Cells.

机构信息

Department of Transfusion Medicine and Haemostaseology, Friedrich-Alexander University of Erlangen-Nuremberg, University Hospital of Erlangen, Erlangen, Germany.

Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.

出版信息

J Immunol. 2024 Jul 15;213(2):115-124. doi: 10.4049/jimmunol.2400036.

Abstract

Human umbilical cord blood (UCB) represents a unique resource for hematopoietic stem cell transplantation for children and patients lacking suitable donors. UCB harbors a diverse set of leukocytes such as professional APCs, including monocytes, that could act as a novel source for cellular therapies. However, the immunological properties of UCB monocytes and monocyte-derived dendritic cells (MoDCs) are not fully characterized. In this study, we characterized the phenotype and functions of UCB-MoDCs to gauge their potential for future applications. UCB exhibited higher frequencies of platelets and lymphocytes as well as lower frequencies of neutrophils in comparison with adult whole blood. Leukocyte subset evaluation revealed significantly lower frequencies of granulocytes, NK cells, and CD14+CD16- monocytes. Surface marker evaluation revealed significantly lower rates of costimulatory molecules CD80 and CD83 while chemokine receptors CCR7 and CXCR4, as well as markers for Ag presentation, were similarly expressed. UCB-MoDCs were sensitive to TLR1-9 stimulation and presented quantitative differences in the release of proinflammatory cytokines. UCB-MoDCs presented functional CCR7-, CXCR4-, and CCR5-associated migratory behavior as well as adequate receptor- and micropinocytosis-mediated Ag uptake. When cocultured with allogeneic T lymphocytes, UCB-MoDCs induced weak CD4+ T lymphocyte proliferation, CD71 expression, and release of IFN-γ and IL-2. Taken together, UCB-MoDCs present potentially advantageous properties for future medical applications.

摘要

人脐带血(UCB)代表了一种独特的造血干细胞移植资源,适用于儿童和缺乏合适供体的患者。UCB 中蕴藏着各种各样的白细胞,如专业的 APC,包括单核细胞,这些细胞可能成为细胞治疗的新来源。然而,UCB 单核细胞和单核细胞衍生的树突状细胞(MoDC)的免疫特性尚未完全确定。在这项研究中,我们对 UCB-MoDC 的表型和功能进行了表征,以评估其未来应用的潜力。与成人全血相比,UCB 表现出更高的血小板和淋巴细胞频率,以及更低的中性粒细胞频率。白细胞亚群评估显示,粒细胞、NK 细胞和 CD14+CD16-单核细胞的频率显著降低。表面标记物评估显示,共刺激分子 CD80 和 CD83 的表达率显著降低,而趋化因子受体 CCR7 和 CXCR4 以及抗原呈递标志物的表达率则相似。UCB-MoDC 对 TLR1-9 的刺激敏感,并在促炎细胞因子的释放方面存在定量差异。UCB-MoDC 具有功能性 CCR7-、CXCR4-和 CCR5 相关的迁移行为,以及足够的受体和胞饮作用介导的抗原摄取。当与同种异体 T 淋巴细胞共培养时,UCB-MoDC 诱导较弱的 CD4+T 淋巴细胞增殖、CD71 表达以及 IFN-γ和 IL-2 的释放。总之,UCB-MoDC 具有未来医学应用的潜在优势。

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