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单独的白细胞介素-4在无粒细胞-巨噬细胞集落刺激因子参与的情况下可将人外周血单核细胞转化为CD1a(弱阳性)、CD83(阳性)的髓样树突状细胞亚群。

IL-4 alone without the involvement of GM-CSF transforms human peripheral blood monocytes to a CD1a(dim), CD83(+) myeloid dendritic cell subset.

作者信息

Roy Keshab Chandra, Bandyopadhyay Gautam, Rakshit Srabanti, Ray Mitali, Bandyopadhyay Santu

机构信息

The Division of Immunology, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.

出版信息

J Cell Sci. 2004 Jul 15;117(Pt 16):3435-45. doi: 10.1242/jcs.01162. Epub 2004 Jun 22.

Abstract

Myeloid dendritic cells (DCs) are conventionally generated by culturing human peripheral blood monocytes in the presence of GM-CSF and IL-4. Here we report that IL-4 alone, in the absence of detectable endogenous GM-CSF, transforms human peripheral blood monocytes to a CD1a(dim) DC subset that could be matured to CD83(+) DCs. Absence of endogenous GM-CSF in IL-4-DC was demonstrated by RT-PCR and flow cytometry. With the exception of CD1a expression, surface marker, morphology and phagocytic activity of these DCs (IL-4-DC) were similar to myeloid DCs (GM-IL-4-DC) conventionally generated in the presence of GM-CSF and IL-4. Conventional GM-IL-4-DC produced less IL-12 compared with IL-4-DC after stimulation with anti-CD40 monoclonal antibody, or LPS plus IFN-gamma, although the difference was more prominent when LPS plus IFN-gamma was used as the stimulus. The GM-IL-4-DC also induced less frequent IFN-gamma(+) T cells in a mixed leukocyte reaction (MLR) than that of IL-4-DC. Yields of IL-4-DCs were marginally lower than that of GM-IL-4-DCs. Our data indicate that peripheral blood monocytes can be transformed to CD1a-deficient myeloid DCs solely by IL-4, and these IL-4-DCs are likely to induce a stronger Th1 response than conventional GM-IL-4-DCs.

摘要

髓样树突状细胞(DCs)通常通过在粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)存在的情况下培养人外周血单核细胞来生成。在此我们报告,在不存在可检测到的内源性GM-CSF的情况下,单独的IL-4可将人外周血单核细胞转化为CD1a(dim)DC亚群,该亚群可成熟为CD83(+)DCs。通过逆转录聚合酶链反应(RT-PCR)和流式细胞术证实了IL-4-DC中不存在内源性GM-CSF。除了CD1a表达外,这些DCs(IL-4-DC)的表面标志物、形态和吞噬活性与在GM-CSF和IL-4存在的情况下常规生成的髓样DCs(GM-IL-4-DC)相似。在用抗CD40单克隆抗体或脂多糖(LPS)加干扰素-γ(IFN-γ)刺激后,常规GM-IL-4-DC产生的IL-12比IL-4-DC少,尽管当使用LPS加IFN-γ作为刺激物时差异更为显著。在混合淋巴细胞反应(MLR)中,GM-IL-4-DC诱导产生IFN-γ(+)T细胞的频率也低于IL-4-DC。IL-4-DCs的产量略低于GM-IL-4-DCs。我们的数据表明,外周血单核细胞仅通过IL-4即可转化为缺乏CD1a的髓样DCs,并且这些IL-4-DCs可能比常规GM-IL-4-DCs诱导更强的Th1反应。

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