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作 者:张新华[1] 钟翠平[1] 周播江[1] 顾云娣[1] 冯久贤[2] 吴超群[3]
机构地区:[1]复旦大学上海医学院解剖与组织胚胎学系,上海200032 [2]上海市胸科医院胸科肿瘤研究所,上海200030 [3]复旦大学生命科学院遗传学研究所,上海200433
出 处:《解剖学报》2004年第2期184-189,共6页Acta Anatomica Sinica
基 金:国家自然科学基金 ( 3 9770 3 87);高校博士点基金( 2 0 0 10 2 460 5 6)资助项目
摘 要:目的 研究人转化生长因子 β1(TGFβ1)基因修饰对大鼠骨髓树突状细胞 (DC)免疫功能的影响。 方法 构建TGFβ1 pcDNA3质粒并转染未成熟DC。检测转染后DC的TGFβ1表达及其功能变化 ,输注 1周后检测TGFβ1 DC在受者脾和淋巴结的分布、T细胞凋亡水平及T细胞端粒酶表达。 结果 TGFβ1 pcDNA3质粒转染DC能有效抑制DC的成熟和分化 ,并下调DC的多种功能。TGFβ1基因转染不仅能降低DC对LPS的反应 ,同时抑制DC在MLR中刺激T细胞增殖的能力。TGFβ1 DC输注受者后 ,1周内可在脾和淋巴结内形成微嵌合 ,并有效诱导T细胞的凋亡 ,抑制T细胞端粒酶的活性和表达。 结论 TGFβ1基因能有效抑制DC的多种功能 ,可用于诱导机体免疫耐受。Objective To detect the effects of human TGFβ1 gene transfection on the immunological functions of rat bone marrow-derived dendritic cells(DC). Methods The immature DC was transfected with recombinant TGFβ1-pcDNA3 mediated by DOTAP. The expression of TGFβ1 on DC was detected and the immunological functions of DC were assayed. The distribution of TGFβ1-DC in recipient rat was observed one week after injection. The apoptosis and the expression of telemerase of T cells in recipient spleen were analyzed. Results TGFβ1-pcDNA3 transfection could inhibit the differentiation and maturation and negatively regulate the immunological functions of DC. The gene modification has not only down-regulated the expression of RT1B on the surface of DC significantly and decreased the response ability of DC to LPS stimulation, but also inhibited the T cell stimulating capacity of DC in MLR. The injected DC was chimerised in the recipient spleen and lymph node one week after injection and could induce apoptosis of T cells. The injected DC could also inhibit the activity and expression of telomerase of T lymphocytes.Conclusion TGFβ1 gene modification obviously inhibited multiple functions and enhanced the tolerogenicity of rat DC.
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