【摘要】 目的　探讨在小鼠树突状细胞 (DC)成熟过程中核因子 κB(NF κB)基因的作用。方法　应用特异性NF κB寡聚脱氧核苷酸诱骗剂 (NF κBODNDecoys)阻断NF κB活性 ,观察DC形态、细胞表面分子表达以及同种T淋巴细胞增殖反应的变化 ,了解NF κB基因对DC成熟及免疫生物活性的影响。结果　NF κBODNDecoys的有效摄取 ,抑制了DC表面共刺激分子CD80、CD86、CD40的表达和白细胞介素 1 2 (IL 1 2 )的分泌 ,阻碍了DC的发育成熟 ,这种阻碍作用不可被脂多糖 (LPS)所逆转。混合淋巴细胞反应显示 ,NF κBODNDecoys的应用可诱导DC刺激同种T淋巴细胞低反应活性 ,抑制了T细胞IL 2和γ 干扰素 (IFN γ)的分泌。结论　NF κB是DC发育成熟过程中关键性调控基因。应用NF κBODNDecoys可抑制DC的成熟 ,从而为生成耐受原性未成熟DC、诱导移植免疫耐受提供了一种新的途径更多还原

【Abstract】 ObjectiveTo investigate the effect of NF-κB on the differentiation and maturation of mu rine bone marrow-derived dendritic cells (DC) in vitro.MethodsThe activity of NF-κB in dendritic cells was blocked by oligodeoxyribonucleot ide Decoys (ODN Decoys) containing two special binding sites for NF-κB. Morpho logical changes of DS were observed. The expression of assistant molecules on th e cell surface was detected by using flow cytometer, and the stimulating activit y of allogeneic T lymphocyte proliferative response was determined in culture mu rine DC. The effect of NF-κB on the maturation and immunobiological activity o f murine DC was studied.ResultsNF-κB ODN Decoys were efficiently incorporated by DC, markedly suppressed the maturation of DC, the expression of assistant costimulatory molecules (CD80, CD8 6 and CD40) on the surface of DC and the secretion of IL-12, blocked the develo pment of DC and this blocked function was not reversed by lipopolysaccharide (LP S). In mixed lymphocyte reactions, DC treated with NF-κB ODN Decoys could indu ce allogeneic T cells hyphoresponsiveness, and this was associated with the inhi bition of Th1-type cytokines (IL-2 and IFN-γ) production.ConclusionsNF-κ B is a key gene to the development and maturation of DC. Specific interference w ith NF-κB in DC using ODN Decoys approaches could offer a novel strategy for i nducing and generating tolerogeneic immature DC and provide a promising means to induce transplant immune tolerance.更多还原