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IL-10对单核来源的DC体外分化发育及功能的抑制效应

The inhibitory repressive effect of IL-10 on the monocyte-derived DC maturation,differation and biological function in vitro

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【作者】 戴俊鲁严朱一蓓吴明媛夏瑜黄勇古涛李敏王勤束永前张学光

【Author】 DAI Jun,LU Yan,ZHU Yi-Bei,WU Ming-Yuan,XIA Yu,HUANG Yong,GU Tao,LI Min,WANG Qin,SHU Yong-Qiang ,ZHANG Xue-Guang.Immunology Department of Medical Biotechnology Institute,Suzhou University,Suzhou 215007,China;Tumor Department of Jiangsu Province People′s Hospital,Nanjing 210009,China

【机构】 苏州大学生物技术研究所江苏省人民医院肿瘤科苏州大学生物技术研究所 苏州215007苏州215007南京210009苏州215007

【摘要】 目的 :研究IL 1 0对单核细胞来源的DC体外发育分化和功能的影响及TNF α和sCD4 0L对IL 1 0抑制DC生物学功能的阻断或逆转效应。方法 :检测经IL 1 0抑制及添加上述干预因素后DC的表型、刺激T细胞增殖和分泌IL 1 2的能力。结果 :IL 1 0能够抑制幼稚DC的成熟 ,促进其向巨噬细胞分化 ,并伴随有DC激发T细胞增殖和分泌IL 1 2能力明显下降 ,这种抑制效应与IL 1 0浓度存在相关性 ;IL 1 0对由sCD4 0L诱导成熟的DC无抑制作用 ,但能抑制TNF α诱导成熟DC分泌IL 1 2的能力 ;在IL 1 0作用后加入TNF α或sCD4 0L均不能逆转IL 1 0对DC抑制作用 ;在IL 1 0作用的同时加入sCD4 0L而不是TNF α ,能完全阻断IL 1 0抑制DC刺激T细胞增殖和分泌IL 1 2的作用。结论 :IL 1 0是肿瘤细胞逃脱免疫攻击的重要因子 ,能够抑制DC的成熟、抗原提呈以及削弱其刺激T细胞增殖的能力等多重负性作用 ,其对由TNF α或sCD4 0L途径诱导成熟的DC的抑制作用不一致 ,CD4 0信号干预对制备肿瘤免疫治疗运用的DC具有重要的价值

【Abstract】 Objective:To investigate the negative effect of the IL-10 on monocyte-derived DC maturation and differation iv vitro,and the potentiation of the TNF-α or sCD40L to inhibit or reverse the IL-10′s inhibitory effect on monocyte-derived DC.Methods:The expression of the surface molecules on DC was detected by FACS analysis.The potentiation to stimulate T cell proliferation was assayed by 3H-TdR incorporation,and IL-12 secretion in the DC supernatant measured by ELISA.Results:In vitro DC-inducing system IL-10 had an obviously negative effect on the maturation as well as the potentiation to stimulate the T cell proliferation and IL-12 secretion of the immature monocyte-derived DC,and IL-10 could drive monocyte-derived DC differentiate into the macrophages.The negative effect was also correlative to the concentration of the added IL-10;The results also showed that IL-10 hadn′t any negative effect on mature DC induced by sCD40L,but to some extent could reduce the mature DC induced by TNF-α to produce IL-12;Furthermore the inhibitory effect of IL-10 can′t be reversed by adding TNF-α or sCD40L after IL-10 was added to the DC-inducing culture system for three days.Interesting by adding sCD40L not TNF-α to the DC-inducing culture system with IL-10 at the same time can inhibit the negative effect of IL-10 completely.Conclusion:IL-10 is an important biological factor produced in tumor microenvironment for escaping the attack of the immune system by repressing maturation,potentiation to costimulate the T cells and IL-12 secretion of the immature monocyte-derived DC.The reverse effect of TNF-α and sCD40L on IL-10 negative effect on monocyte-derived was different.All together suggested that CD40 signal has important values to obtain the therapeutic DC for the tumor immune intervention.

【关键词】 IL-10TNF-αsCD40L树突状细胞肿瘤免疫
【Key words】 IL-10TNF-αsCD40LDendritic cellTumor immunity
【基金】 江苏省重点科研基金资助项目 ( 2 0 0 10 0 7) ;江苏省重点实验室项目 ;苏州大学医学发展资金资助
  • 【文献出处】 中国免疫学杂志 ,Chinese Journal of Immunology , 编辑部邮箱 ,2004年06期
  • 【分类号】R392
  • 【被引频次】6
  • 【下载频次】123
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