[关键词]
[摘要]
目的: 探讨不同因素对人外周血单核细胞来源的树突状细胞(DC)体外分化成熟的影响。方法:通过流式细胞仪表型分析、混合淋巴细胞反应、抗原摄取能力检测、DC对T细胞的趋化能力及对IL-10的拮抗效应的测定,研究了TNF-α,FL,sCD40L,CD40mAb,gp130,IL-10等不同因素对DC的体外分化成熟及功能的影响。结果:CD40信号和TNF-α都可以有效地使DC上调表达共刺激分子CD80,CD86并进而促进DC激发T细胞的增殖和活化及对T淋巴细胞的趋化作用,但在体外培养体系中,sCD40L能有效地拮抗IL-10的抑制效应,而TNF-α则明显不如sCD40L有效;激发型gp130单克隆抗体和人重组FL可以显著地促进DC的体外扩增,但是无明显地促进DC分化成熟和促进DC激发T细胞的功能。结论:CD40和TNF-α都具有促进DC分化、成熟的能力,但CD40的作用明显优于TNF-α。
[Key word]
[Abstract]
Objective:To study the affecting factors on the differentiation, maturation and function on the human peripheral blood monocyte-derived dendritic cells (DC). Methods:Through DCs′ surface molecules analysis, mixed-lymphocyte reaction, FITC-Dextran capture, cell counting and chemotaxis activity of T lymphocytes, we compared functions of DC stimulated with different cytokines including TNF-α, FL, sCD40L, CD40mAb,gp130 and IL-10. Results:Both CD40- and TNF-α signalling are able to promote differentiation and maturation of DC, including upregulation of costimulatory molecules expression, such as CD80 and CD86, enhancement of DC-mediated MLR, promotion of T cell chemotactic ability to DC; CD40 signalling counteracted the inhibitory effects of IL-10 on DC more efficiently than TNF-α signalling; The agonist gp130 mAb and human recombinant FL can remarkably promote the proliferation of DC in vitro, while there are no distinct effects on DCs′ differentiation, maturation and ability to activate T cells.Conclusions: CD40 signalling is more powerful than TNF-α, and plays a unique role to abtain more mature and functional DC in vitro.
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[基金项目]
江苏省医学重点实验室、江苏省卫生厅科研基金(H20010)及江苏省卫生厅科技重大攻关项目(H200211)