干扰素α对慢性髓系白血病来源树突状细胞表达Th细胞因子和CCR7的影响(英文)

Influences of Interferon-α on Expression of Th Cytokines and CCR7 in Dendritic Cells from Patients with Chronic Myeloid Leukemia In Vitro

本研究探讨干扰素α(IFN-α)对慢性髓系白血病(CML)来源树突状细胞(DC)表达趋化因子CCR7及分泌IL-10、IL-12P70的影响。在诱导CML-DCs的无血清条件培养基中,除加入SCF、GM-CSF、TNF-α及IL-4外,还加入不同浓度IFN-α。培养10-14天后,用流式细胞术检测共刺激分子及CCR7表达,G显带法显示Ph1染色体,噻唑蓝(MTT)法检测CML-DC刺激正常人外周血淋巴细胞增殖状况,ELISA法检测培养上清IL-10及IL-12P70含量。结果显示:IFN-α(300U/ml)组与无IFN-α组比较其CML-DC的CD40、CD83、CD86及CCR7的表达均升高1倍,异体混合淋巴细胞反应(MLR)中OD值增加1倍,Ph1染色体阳性比例及IL-10和IL-12P70浓度均减低。结论:IFN-α能够部分纠正CML-DC免疫表型及功能缺陷,这同其上调DC共刺激分子和CCR7表达及解除了CML血清中IL-10对CML-DC分化的抑制有关。

This study was aimed to investigate the influences of interferonα （IFN-α） on expressions of CCR7 , inter- leukin10 （IL-10） and IL-12p70 in dendritic cells （DCs） from patients with chronic myeloid leukemia （CML）. In addition to stem cell factor （ SCF）, granulocyte-macrophage colony stimulating factor （ GM-CSF）, tumor necrosis factor-α （TNF-α） and IL-4, IFN-α was added to the serum-free medium of DCs. After culture for 10 - 14 days, phenotypes and function of CML-DCs were evaluated respectively by flow cytometry and methyl thiazolyl tetrazoIum （MTT） assay. Chromosome of DCs was analyzed by displaying G banding assay. The concentrations of IL-10 and IL-12P70 in supcrnatants were evaluated by enzyme-Inked immunosorbent assay （ELISA）. The results showed that the expressions of CD40, CD83, CD86 and CCR7 and the OD value in allogeneic mixed-lymphocyte reaction （MLR） in group with IFN-α （300 U/ml） were twice as high as those in group without IFN-α. The percentage of Ph1 positive ceils and concentrations of IL-10 and IL-12 P70 were reduced in group with IFN-α. It is concluded that the defective phenotypes and functions of CML-DCs can be recruited partly by IFN-α. The mechanism may lie in the facts that expression of CCR7 and co-stimulatory molecules is promoted and the inhibitory effect of IL-10 on CML-DCs is relieved partly through the regulation of IFN-α.