低剂量粒细胞巨噬细胞集落刺激因子诱导的小鼠骨髓未成熟树突状细胞抗成熟特性的研究

Study on the anti-maturation features of immature dendritic cells induced by low dosage of granulocyte macrophage colony stimulating factor

目的 观察内毒素 /脂多糖 (LPS)、肿瘤坏死因子α(TNF α)、干扰素γ(IFN γ)等促成熟物质对低剂量粒细胞巨噬细胞集落刺激因子 (rmGM CSF)诱导的小鼠骨髓未成熟树突状细胞 (DC)成熟特性的影响。 方法 制备小鼠骨髓细胞 ,分别用不同剂量rmGM CSF培养 ,6d后收集悬浮细胞进行检测。用LPS、TNF α、IFN γ与小剂量rmGM CSF培养获得的DC(GMlowDC)共同孵育 3d后 ,行混合淋巴细胞反应 ,观察其诱导未致敏脾淋巴细胞增殖的情况 ,并与大剂量rmGM CSF培养获得的DC(GMhighDC)进行比较。 结果 GMlowDC不能激活未致敏脾淋巴细胞 ,且在与LPS、TNF α和IFN γ共同培养 3d后 ,仍不能有效诱导未致敏脾淋巴细胞增殖 ,刺激指数 (SI)均 <2 .0 0 ;而GMhighDC刺激未致敏脾淋巴细胞增殖的能力较强 ,SI为 4 .71。 结论 GMlowDC具有对LPS、TNF α和IFN γ刺激不敏感的抗成熟特性。

Objective To investigate the influence of maturative agents,including lipopolysaccharide (LPS), tumor necrosis factor α(TNF-α) and interferon γ(IFN-γ)on the maturation of immature dendritic cells originated from murine bone marrow induced by low dose of granulocyte macrophage colony stimulating factor(rm GM-CSF). Methods Dendritic cells from murine bone marrow progenitors were cultured in low and high doses of GM-CSF for 6 days ,and then the suspending cells were harvested for the experiment. After 3 days of co-culture of the obtained DC with low dose rmGM-CSF(GM lowDC) with LPS,TNF-α and IFN-γ, the stimulatory capacity of inducing proliferation of non-sensitized splenocytes of GM lowDC in mixed lymphocyte reaction (MLR) was observed and compared with that of GM highDC. Results GM lowDC could not activate the non-sensitized splenocytes or induce it into proliferation after 3 days of co-incubation with LPS, TNF-α,IFN-γ, with the stimulation index(SI) lower than 2. Whereas GM highDC could strongly activate naive splenocytes (SI=4.71). Conclusion GM lowDC was resistant to maturation and insensitive to the stimulation by LPS,TNF-α or IFN-γ.