Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell characteristics.
Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell characteristics.
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DOI：
10.1084/jem.187.7.1019
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发表时间：
1998-04-06
期刊：
影响因子：
--
通讯作者：
Knapp W
中科院分区：
文献类型：
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作者：
Oehler L;Majdic O;Pickl WF;Stöckl J;Riedl E;Drach J;Rappersberger K;Geissler K;Knapp W
多形粒细胞（PMN）被认为主要通过吞噬作用和细胞毒性化合物的释放来实现其在宿主防御中的作用，并且在抗原呈递和特异性T细胞的刺激中是低效的。相反，树突状细胞（DC）是有效的抗原呈递细胞，具有启动初级免疫应答的独特能力。我们在这里证明，高度纯化的乳铁蛋白阳性的直接前体的终末期嗜中性粒细胞（PMNp）可以在其功能成熟程序中被逆转，并被驱动以获得特征性的DC功能。在与细胞因子组合粒细胞/巨噬细胞集落刺激因子+白细胞介素4+肿瘤坏死因子α培养后，它们形成DC形态并获得DC的分子特征。这些分子变化包括DC相关表面分子分化簇（CD）1a、CD 1b、CD 1c、人白细胞抗原（HLA）-DR、HLA-DQ、CD 80、CD 86、CD 40、CD 54和CD 5的新表达，以及CD 15和CD 65 s的下调。用CD 40配体的额外刺激也诱导CD 83的表达并上调CD 80、CD 86和HLA-DR。嗜中性粒细胞衍生的DC在同种异体以及自体混合淋巴细胞反应（MLR）中是有效的T细胞刺激物，而新鲜分离的中性粒细胞完全不能这样做。此外，与新鲜分离的单核细胞相比，嗜中性粒细胞衍生的DC在向自体T细胞呈递可溶性抗原方面的效率高至少10，000倍。此外，在功能方面，这些嗜中性粒细胞衍生的DC因此非常类似于“经典”DC群体。
Polymorphonuclear granulocytes (PMNs) are thought to fulfill their role in host defense primarily via phagocytosis and release of cytotoxic compounds and to be inefficient in antigen presentation and stimulation of specific T cells. Dendritic cells (DCs), in contrast, are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. We demonstrate here that highly purified lactoferrin-positive immediate precursors of end-stage neutrophilic PMN (PMNp) can be reverted in their functional maturation program and driven to acquire characteristic DC features. Upon culture with the cytokine combination granulocyte/macrophage colony-stimulating factor plus interleukin 4 plus tumor necrosis factor α, they develop DC morphology and acquire molecular features characteristic for DCs. These molecular changes include neo-expression of the DC-associated surface molecules cluster of differentiation (CD)1a, CD1b, CD1c, human leukocyte antigen (HLA)-DR, HLA-DQ, CD80, CD86, CD40, CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with CD40 ligand induces also expression of CD83 and upregulates CD80, CD86, and HLA-DR. The neutrophil-derived DCs are potent T cell stimulators in allogeneic, as well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolated neutrophils are completely unable to do so. In addition, neutrophil-derived DCs are at least 10,000 times more efficient in presenting soluble antigen to autologous T cells when compared to freshly isolated monocytes. Also, in functional terms, these neutrophil-derived DCs thus closely resemble “classical” DC populations.