Murine plasmacytoid pre-dendritic cells generated from Flt3 ligand-supplemented bone marrow cultures are immature APCs
Murine plasmacytoid pre-dendritic cells generated from Flt3 ligand-supplemented bone marrow cultures are immature APCs
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DOI：
10.4049/jimmunol.169.12.6711
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发表时间：
2002-12-15
影响因子：
4.4
通讯作者：
De Smedt, T
中科院分区：
文献类型：
--
作者：
Brawand, P;Fitzpatrick, DR;De Smedt, T
在小鼠模型中，在体内和最近在体外培养系统中描述了人浆细胞样前细胞（PDC）的假定对应物。在这项研究中，我们报告说，可以用FLT3配体（FL）生成大量的骨髓衍生的鼠CD11C（+）B220 B220（+）PDC作为唯一的外源分化/生长因子，并且PDC在体内受到体内调节PDC的产生。 FL，因为缺乏FL的小鼠显示脾脏PDC数量大大减少。我们广泛分析了骨髓来源的CD11C（+）B220（+）PDC，并根据MHC II，激活标记和趋化因子受体表达水平描述了其未成熟的APC表型。 CD11C（+）B220（+）PDC显示出与经典CD11C（+）B220（ - ）树突状细胞不同的非重叠电话样受体模式，并且是T细胞刺激剂不良。刺激含有某些CPG基序的寡脱氧核苷酸加上CD40配体加上CD40配体加GM-CSF的CD11C（+）B220（+）PDC，导致MHC II，CD80，CD86和CD8ALPHA表达水平增加，从迁移到IFN-Alpha和IL-12分泌，并获得CD4（+）和CD8（+）OVA特异性TCR转基因幼体T细胞的启动能力。因此，鼠PDC的体外产生可能是进一步研究PDC生物学以及这些细胞在病毒免疫和其他环境中的潜在作用的有用工具。
The putative counterparts of human plasmacytoid pre-dendritic cells (pDCs) have been described in vivo in mouse models and very recently in an in vitro culture system. In this study, we report that large numbers of bone marrow-derived murine CD11c(+)B220(+) pDCs can be generated with Flt3 ligand (FL) as the sole exogenous differentiation/growth factor and that pDC generation is regulated in vivo by FL because FL-deficient mice showed a major reduction in splenic pDC numbers. We extensively analyzed bone marrow-derived CD11c(+)B220(+) pDCs and described their immature APC phenotype based on MHC class II, activation markers, and chemokine receptor level of expression. CD11c(+)B220(+) pDCs showed a nonoverlapping Toll-like receptor pattern of expression distinct from that of classical CD11c(+)B220(-) dendritic cells and were poor T cell stimulators. Stimulation of CD11c(+)B220(+) pDCs with oligodeoxynucleotides containing certain CpG motifs plus CD40 ligand plus GM-CSF led to increased MHC class II, CD80, CD86, and CD8alpha expression levels, to a switch in chemokine receptor expression that affected their migration, to IFN-alpha and IL-12 secretion, and to the acquisition of priming capacities for both CD4(+) and CD8(+) OVA-specific TCR-transgenic naive T cells. Thus, the in vitro generation of murine pDCs may serve as a useful tool to further investigate pDC biology as well as the potential role of these cells in viral immunity and other settings.