Interleukin-3 and interferon β cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties
Interleukin-3 and interferon β cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties
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DOI：
10.1182/blood.v99.3.993
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发表时间：
2002-02-01
期刊：
影响因子：
20.3
通讯作者：
Goldman, M
中科院分区：
文献类型：
--
作者：
Buelens, C;Bartholomé, EJ;Goldman, M
观察到干扰素β（IFN-β）阻止白细胞介素-3受体α链（IL-3R α）的下调，这在人单核细胞培养期间自发发生。通过IL-3拯救IFN-β处理的单核细胞免于凋亡的事实证明了IL-3R的功能性。在IFN-β和IL-3存在下培养的单核细胞获得树突状形态，并表达高水平的HLA抗原I类和II类以及共刺激分子。当由脂多糖或表达CD 40配体（CD 40 L）的成纤维细胞转染子刺激时，与在IL-4和粒细胞-巨噬细胞集落刺激因子（GM-CSF）中产生的树突状细胞（DC）相比，在IFN-β和IL-3中产生的DC分泌高水平的IL-6、IL-8和肿瘤坏死因子-α，但分泌低水平的IL-12。在混合白细胞培养中，IL-3-IFN-β DCs诱导同种异体脐带血T细胞的强烈增殖反应，并诱导幼稚成人CD 4（+）T细胞产生高水平的IFN-γ和IL-5。最后，发现IL-3-IFN-β DC响应于Poly（I：C）而不是流感病毒产生比IL-4-GM-CSF DC高得多的IFN-α水平。结论是，在IL-3和IFN-β存在下培养的单核细胞分化成具有有效辅助性T细胞刺激能力的DC，尽管它们的IL-12分泌低。(C)2002年，美国血液学会。
It was observed that interferon beta (IFN-beta) prevents the down-regulation of the interleukin-3 receptor alpha chain (IL-3Ralpha), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-beta and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules. When stimulated by either lipopolysaccharide or fibroblasts expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs) generated in IFN-beta and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-alpha but low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3-IFN-beta DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-gamma and IL-5 by naive adult CD4(+) T cells. Finally, IL-3-IFN-beta DCs were found to produce much higher levels of IFN-alpha than IL-4-GM-CSF DCs in response to Poly (I:C) but not to influenza virus. It was concluded that monocytes cultured in the presence of IL-3 and IFN-beta differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12. (C) 2002 by The American Society of Hematology.