de Saint-Vis B, Fugier-Vivier I, Massacrier C, Gaillard C, Vanbervliet B, Aït-Yahia S, Banchereau J, Liu Y J, Lebecque S, Caux C
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
J Immunol. 1998 Feb 15;160(4):1666-76.
In the present study, we have analyzed the pattern of cytokines expressed by two independent dendritic cell (DC) subpopulations generated in vitro from human cord blood CD34+ progenitors cultured with granulocyte-macrophage CSF and TNF-alpha. Molecularly, we confirmed the phenotypic differences discriminating the two subsets: E-cadherin mRNA was only detected in CD1a+-derived DC, whereas CD68 and factor XIIIa mRNAs were observed exclusively in CD14+-derived DC. Semiquantitative reverse-transcriptase PCR analysis revealed that both DC subpopulations spontaneously expressed IL-1alpha, IL-1beta, IL-6, IL-7, IL-12 (p35 and p40), IL-15, IL-18, TNF-alpha, TGF-beta, macrophage CSF, and granulocyte-macrophage CSF, but not IL-2, IL-3, IL-4, IL-5, IL-9, and IFN-gamma transcripts. Both subpopulations were shown to secrete IL-12 after CD40 triggering. Interestingly, only the CD14+-derived DC secreted IL-10 after CD40 activation, strengthening the notion that the two DC subpopulations indeed represent two independent pathways of DC development. Furthermore, both DC subpopulations expressed IL-13 mRNA and protein following activation with PMA-ionomycin, but not with CD40 ligand, in contrast to IL-12 and IL-10, revealing the existence of different pathways for DC activation. Finally, we confirmed the expression of IL-7, IL-10, and IL-13 mRNA by CD4+ CD11c+ CD3- DC isolated ex vivo from tonsillar germinal centers. Thus, CD14+-derived DC expressing IL-10 and factor XIIIa seemed more closely related to germinal center dendritic cellsGCDC than to Langerhans cells.
在本研究中，我们分析了由人脐血CD34 +祖细胞在体外与粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）和肿瘤坏死因子 - α（TNF - α）共同培养产生的两个独立树突状细胞（DC）亚群所表达的细胞因子模式。在分子水平上，我们证实了区分这两个亚群的表型差异：E - 钙黏蛋白mRNA仅在CD1a +衍生的DC中检测到，而CD68和因子XIIIa mRNA仅在CD14 +衍生的DC中观察到。半定量逆转录 - 聚合酶链反应（RT - PCR）分析显示，两个DC亚群均自发表达白细胞介素 - 1α（IL - 1α）、白细胞介素 - 1β（IL - 1β）、白细胞介素 - 6（IL - 6）、白细胞介素 - 7（IL - 7）、白细胞介素 - 12（p35和p40）、白细胞介素 - 15（IL - 15）、白细胞介素 - 18（IL - 18）、肿瘤坏死因子 - α（TNF - α）、转化生长因子 - β（TGF - β）、巨噬细胞集落刺激因子（M - CSF）和粒细胞 - 巨噬细胞集落刺激因子（GM - CSF），但不表达白细胞介素 - 2（IL - 2）、白细胞介素 - 3（IL - 3）、白细胞介素 - 4（IL - 4）、白细胞介素 - 5（IL - 5）、白细胞介素 - 9（IL - 9）和干扰素 - γ（IFN - γ）转录本。两个亚群在CD40触发后均显示分泌白细胞介素 - 12。有趣的是，只有CD14 +衍生的DC在CD40激活后分泌白细胞介素 - 10，这强化了这两个DC亚群确实代表DC发育的两个独立途径的观点。此外，与白细胞介素 - 12和白细胞介素 - 10相反，两个DC亚群在用佛波酯 - 离子霉素（PMA - ionomycin）激活后表达白细胞介素 - 13 mRNA和蛋白，但用CD40配体激活时不表达，这揭示了DC激活存在不同途径。最后，我们证实了从扁桃体生发中心离体分离的CD4 + CD11c + CD3 - DC表达白细胞介素 - 7、白细胞介素 - 10和白细胞介素 - 13 mRNA。因此，表达白细胞介素 - 10和因子XIIIa的CD14 +衍生的DC似乎与生发中心树突状细胞（GCDC）比与朗格汉斯细胞更密切相关。
