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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Stimulatory and inhibitory differentiation of human myeloid dendritic cells.
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Stimulatory and inhibitory differentiation of human myeloid dendritic cells.

机译：人骨髓树突状细胞的刺激性和抑制性分化。

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摘要

Dendritic cells (DCs) play a critical obligate role in presenting antigens to T cells for activation. In the process, upon antigen capture, DCs undergo maturation and become more stimulatory. Human myeloid DCs can be generated from various sources, including blood, bone marrow, and CD34(+) stem cells. As such, plastic-adherent monocytes from circulation have served as a ready source for generating myeloid DCs in culture in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for translational research in active specific immunotherapy, especially in cancer, with the belief that they are essentially stimulatory or "immunogenic." Here we show that in vitro cultures of plastic-adherent circulating monocytes in GM-CSF and IL-4 followed by further maturation in interferon-gamma plus bacterial superantigens (DC maturing agents) can give rise to two diametrically opposite types of DCs-one stimulatory and another inhibitory. The stimulatory DCs express higher amounts of costimulatory molecules, synthesize IL-12, and efficiently stimulate naive allogeneic T cells in mixed lymphocyte reaction (MLR). The inhibitory DCs, in contrast, express lower concentrations of the critical costimulatory molecules, synthesize large amounts of IL-10, and are nonstimulatory in allogeneic primary MLR. Moreover, while the stimulatory DCs further amplify proliferation of T cells in lectin-driven proliferation assays, the inhibitory DCs totally block T cell proliferation in similar assays, in vitro. Most interestingly, neutralization of the endogenously derived IL-10 with anti-IL-10 antibody in DC cultures repolarizes the inhibitory DCs toward stimulatory phenotype. Accordingly, these observations have important implications in translational research involving myeloid DCs. Copyright 2000 Academic Press.
机译：树突状细胞（DC）在将抗原呈递给T细胞进行活化方面起着至关重要的作用。在此过程中，抗原捕获后，DC会成熟并变得更具刺激性。人骨髓DC可以从各种来源生成，包括血液，骨髓和CD34（+）干细胞。这样，来自循环的可粘附塑料的单核细胞已成为在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白介素-4（IL-4）中培养产生DC的现成来源，用于主动特异性免疫疗法的翻译研究，尤其是在癌症中，并认为它们本质上是刺激性的或“免疫原性的”。在这里，我们显示了在GM-CSF和IL-4中粘附于塑料的循环单核细胞的体外培养，然后在干扰素-γ加上细菌超抗原（DC成熟剂）中进一步成熟，可以产生两种截然相反的DCs。和另一种抑制作用。刺激性DCs表达大量的共刺激分子，合成IL-12，并有效地刺激混合淋巴细胞反应（MLR）中的天然同种T细胞。相反，抑制性DC表达较低浓度的关键共刺激分子，合成大量IL-10，并且在同种异体原代MLR中无刺激性。此外，尽管在凝集素驱动的增殖试验中刺激性DC进一步放大了T细胞的增殖，但在相似的体外试验中，抑制性DC完全阻断了T细胞的增殖。最有趣的是，在DC培养物中用抗IL-10抗体中和内源性IL-10将抑制性DC重新极化为刺激表型。因此，这些观察结果对涉及髓系DC的翻译研究具有重要意义。版权所有2000学术出版社。

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