人CD34+ CD11b-脐带血干细胞在体外产生一个CD34- CD11b+亚群，该亚群富含朗格汉斯蛋白阳性的朗格汉斯树突状细胞前体。

Human CD34+ CD11b- cord blood stem cells generate in vitro a CD34- CD11b+ subset that is enriched in langerin+ Langerhans dendritic cell precursors.

作者信息

Soulas Caroline, Arrighi Jean-François, Saeland Sem, Chapuis Bernard, Kindler Vincent

机构信息

Division of Hematology, Geneva University Hospital, Geneva, Switzerland.

出版信息

Exp Hematol. 2006 Nov;34(11):1471-9. doi: 10.1016/j.exphem.2006.06.011.

DOI:10.1016/j.exphem.2006.06.011

PMID:17046566

Abstract

OBJECTIVE

We investigated whether the expression of CD11b on precursors derived in vitro from CD34+ hematopoietic stem cells was related to their ability to generate CD11b- and CD11b+ Langerhans dendritic cells (LC).

METHODS

Human CD34+ cells purified from cord blood were cultured with FLT3 ligand, thrombopoietin, and stem cell factor (FTS) for 2 weeks, analyzed, and sorted by FACS. Sorted fractions were cultured as above, or differentiated into LC with GM-CSF, IL-4, and TGF-beta1 (G4-TGF) for 6 days. The capacity of LC to internalize langerin and dextran was assessed.

RESULTS

Ex vivo, human CD34+ cells were CD11b- and mostly CLA+. After 2 weeks of culture with FTS, CD34- CLA- CD11b- and CD34- CLA- CD11b+ cells emerged. CD11b- cells were the most ancestral because they were the only ones to proliferate with FTS, and constantly generated CD11b+ cells. Both CD11b- and CD11b+ sorted cells generated E-cadherin+ langerin+ LC after incubation with G4-TGF. The former fraction contained 46% +/- 15% of E-cadherin+ and 10% +/- 5% of langerin+ cells, whereas in the latter fraction these values reached respectively 66% +/- 23% and 30% +/- 16% (mean +/- SD, n = 7, p < 0.056). Looking at functional properties, CD11b- and CD11b+ LC were similar in terms of langerin and dextran endocytosis. By contrast, only CD11b+ LC internalized fluorescent LPS.

CONCLUSION

Human CD34+ CD11b- cells differentiate in FTS culture into a CD34- CD11b- precursor that in turn generates CD34- CD11b+ cells. These cells are enriched in LC precursors compared to CD34- CD11b- cells. Both CD11b- and CD11b+ LC are generated in vitro, and each fraction may assume different functions in inflammatory situations.

摘要

目的

我们研究了体外从CD34⁺造血干细胞衍生的前体细胞上CD11b的表达是否与其产生CD11b⁻和CD11b⁺朗格汉斯树突状细胞（LC）的能力相关。

方法

从脐带血中纯化的人CD34⁺细胞与FLT3配体、血小板生成素和干细胞因子（FTS）一起培养2周，进行分析并通过流式细胞术分选。分选的组分按上述方法培养，或用GM-CSF、IL-4和TGF-β1（G4-TGF）分化成LC 6天。评估LC内化朗格素和葡聚糖的能力。

结果

在体外，人CD34⁺细胞是CD11b⁻且大多为CLA⁺。用FTS培养2周后，出现了CD34⁻CLA⁻CD11b⁻和CD34⁻CLA⁻CD11b⁺细胞。CD11b⁻细胞是最原始的，因为它们是唯一能与FTS增殖并不断产生CD11b⁺细胞的细胞。与G4-TGF孵育后，CD11b⁻和CD11b⁺分选细胞均产生E-钙黏蛋白⁺朗格素⁺LC。前一组分中E-钙黏蛋白⁺细胞占46%±15%，朗格素⁺细胞占10%±5%，而后一组分中这些值分别达到66%±23%和30%±16%（平均值±标准差，n = 7，p < 0.056）。从功能特性来看，CD11b⁻和CD11b⁺LC在朗格素和葡聚糖内吞作用方面相似。相比之下，只有CD11b⁺LC内化荧光脂多糖。