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

作　　者：戴俊[1] 鲁严[1] 朱一蓓[1] 吴明媛[1] 夏瑜[1] 黄勇[1] 古涛[1] 李敏[1] 王勤[1] 束永前[2] 张学光[1] 

机构地区：[1]苏州大学生物技术研究所,苏州215007 [2]江苏省人民医院肿瘤科,南京210009

出　　处：《中国免疫学杂志》2004年第6期384-388,共5页Chinese Journal of Immunology

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

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 ,CD4Objective: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-10 TNF-A SCD40L 树突状细胞 肿瘤免疫 

分 类 号：R392[医药卫生—免疫学]