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M蛋白致敏树突状细胞诱导的抗骨髓瘤细胞效应
刘军民,李玉峰,宣恒报,李媛媛,邓之奎,LIUJun-min,LIYu-feng,XUANHen-bao,LIYuan-yuan,DENGZhi-kui
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摘要:
目的:探讨M蛋白致敏树突状细胞(DC)诱导激活的自体T细胞对骨髓瘤细胞特异性免疫杀伤效应.方法:取多发性骨髓瘤(MM)患者外周血单核细胞经GM-CSF、IL-4和TNF-α体外联合诱导生成DC,用DEAE-纤维素提取法自MM患者血清中分离、纯化M蛋白.以M蛋白冲击致敏DC(同时设未致敏的DC为对照),流式细胞术分析DC免疫表型,并与自体T淋巴细胞进行混合淋巴细胞反应.51Cr释放法测定T细胞对不同靶细胞(患者骨髓瘤细胞、U266细胞)的杀伤活性.结果:经M蛋白致敏的DC激发自体T细胞增殖的能力明显强于未致敏的DC(P<0.05);同时负载M蛋白DC激活的T细胞杀伤活性也明显强于对照组(P<0.01),而两组T细胞对U266细胞均无明显杀伤活性.结论:M蛋白致敏DC能有效诱导自体T细胞对骨髓瘤细胞的特异性杀伤作用.
关键词:  多发性骨髓瘤、M蛋白、树突细胞、T淋巴细胞
DOI:10.3724/SP.J.1008.2006.00624
投稿时间:2005-12-09修订日期:2006-04-05
基金项目:江苏省淮安市医学科研计划项目(WX200505).
Myeloma protein-pusled dendritic cells induced anti-myeloma cells activity
刘军民,李玉峰,宣恒报,李媛媛,邓之奎,LIU Jun-min,LI Yu-feng,XUAN Hen-bao,LI Yuan-yuan,DENG Zhi-kui
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Abstract:
Objective: To investigate the anti-myeloma cells specific immune activity induced by myeloma protein-pusled dendritic cells(DCs). Methods: DCs were obtained from peripheral blood(PB) of multiple myeloma(MM) patients after co-culture with GM-CSF,IL-4 and TNF-α. The phenotype of DCs was examined by flow cytometry. Host lymphocytes were stimulated with DCs pulsed with myeloma protein acquired from serum of MM patients on DEAE-celluose; lymphocytes treated with unpulsed-DC served as control. [^3 H]-thymidine incorporation and 4 h ^51 Cr-release assay were used to detect the proliferation and cytotoxicity against different targets(auto-myeloma cells,U266 cells) by T lymphocytes. Results: In vitro proliferation and cytotoxicity of T lymphocytes activated by myeloma protein pulsed-DCs were greater than those of T lymphocytes in the control group(P〈0.01). T lymphocytes in neither of the 2 groups had notable cytotoxicity against U266 cells. Conclusion: DCs pulsed by myeloma protein can effectively induce specific cytotoxicity of T lymphocytes against myeloma cells
Key words:  multiple myeloma  myeloma protein  dendritic cells  T-lymphocytes