Interferon-alpha induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo.
Interferon-alpha induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo.
复制标题
干扰素-α 在体外和体内诱导 CML 单核细胞的树突状细胞分化。
作者：
R. Paquette;N. Hsu;J. Said;M. Mohammed;N. Rao;G. Shih;G. Schiller;C. Sawyers;J. Glaspy
本研究评价了干扰素-α（IFN-α）诱导慢性粒细胞白血病（CML）树突状细胞（DC）分化的能力。用IFN-α和粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养的CML患者外周血单核细胞形成树突状形态。荧光原位杂交结果显示DC中存在bcr/abl易位。用IFN-α/GM-CSF制备的DC表达的I类和II类HLA水平显著高于在白细胞介素-4（IL-4）和GM-CSF中生长的DC。使用IFN-α/GM-CSF从新诊断的CML患者制备的DC表达与正常DC相当的免疫调节蛋白水平。与此相反，从CML患者培养的DCs谁没有实现对IFN-α的细胞遗传学应答表达显着较低水平的I类HLA，CD 40，CD 54，CD 80和CD 86比正常的DCs。CD 86的表达在与IFN-α/IL-4/GM-CSF共同培养或经IFN-α/GM-CSF处理的细胞经CD 40配体诱导成熟时增强。在同种异体混合白细胞反应中，IFN-α失败的DC比正常DC刺激性低。对IFN-α有细胞遗传学应答的CML患者最初的骨髓DC数量较少，随着治疗显著增加，而无应答者在基线时的DC更普遍，没有显示出与治疗一致的变化。因此，IFN-α可以在体外和体内诱导CML祖细胞向DC分化。IFN-α在CML中的治疗活性可能是由于其刺激能够呈递CML特异性抗原的DC的产生的能力。当DC分化受损时，可能导致对IFN-α的抗性。
The ability of interferon-alpha (IFN-alpha) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CML) was evaluated. Peripheral blood mononuclear cells from CML patients cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/abl translocation. The DCs prepared with IFN-alpha/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFN-alpha/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-alpha expressed significantly lower levels of class I HLA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CML DCs was enhanced when they were cultured with IFN-alpha/IL-4/GM-CSF, or when IFN-alpha/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-alpha failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CML patients who had a cytogenetic response to IFN-alpha initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-alpha can induce DC differentiation from CML progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-alpha in CML may be due to its ability to stimulate the generation of DCs that can present CML-specific antigens. Resistance to IFN-alpha may result when DC differentiation becomes impaired.