ICOS/ICOSL逆向信号诱导成熟过程中树突状细胞特异性分泌TGF-β1  

Increasing TGF-β1 by dendritic cells during its maturation induced by ICOS/ICOSL reverse signal

作　　者：唐古生[1] 张薇薇[1] 吴君[1] 沈茜[1] 

机构地区：[1]第二军医大学附属长海医院实验诊断科,上海200433

出　　处：《中国免疫学杂志》2011年第6期502-506,510,共6页Chinese Journal of Immunology

摘　　要：目的:分析可诱导共刺激分子(ICOS)能否向成熟过程中树突状细胞(DCs)传递逆向信号及其对DCs功能的影响。方法:取小鼠骨髓细胞,体外诱导培养、纯化第5天不成熟DCs,以ICOSIg或对照IgG加LPS或CpG处理后,流式细胞仪检测DCs表型分子、吞噬功能及胞内细胞因子改变;以ELISA检测培养上清细胞因子变化;以[3H]-TdR掺入法探讨DCs抗原递呈功能。结果:与IgG对照组相比,ICOSIg联合LPS或CpG处理组DCs分泌TGF-β1的表达明显升高;ICOSIg作用于成熟过程中DCs,其吞噬功能与对照IgG相比近似或略有增强,但其抗原递呈功能受到部分抑制,可引起T细胞中IL-2、IL-10明显升高。结论:ICOS作用于成熟过程中的DCs后,促进DCs特异性分泌TGF-β1、部分抑制了DCs的抗原递呈功能,其机制可能是诱导了产IL-10 CD4+T细胞的生成;这种反向信号在不同机制诱导DCs成熟的过程中均可能存在。Objective：To determine whether ICOS could deliver any reverse signals through ICOSL expressed on mouse-derived dendritic cells（DCs） during their maturation and to detail their possible characteristics. Methods： The five-day immature DCs were generated and purified from mice bone marrow mononuclear cells as previous described. DCs were then divided into groups and treated by ICOSIg or IgG together with LPS or CpG. The surface phenotype molecules, the ability of phagocytosis of DCs and intracellular cytokines of T cells were determined by flow cytometry; cytokines in supematant were detected by ELISA; [^3H ]TdR thymine incorporation was used for analysis of antigen presentation. Results：When treated with ICOSIg together with lipopolysaccharide （LPS） or mouse CpG, DCs showed an dose-dependent secretion of TGF-131 compared to those in the IgG control groups. These modified maturing DCs partially lost their ability of antigen presentation, but induced more IL-10-producing antigen-specific CD4^＋ T cells in vitro as determined by ELISA and intracellalar cytokines detection. Conclusion： Reverse signal to DCs by ICOS during their maturation induces a specific elevation of TGF-β1, which might cause an elevation of IL-l0-producing CD4^＋ T cells.This kind of reverse signal might be universal during the maturation of DCs caused by different mechanisms, such as LPS or CpG. These findings might also throw a new light on the complicated network of receptor-ligand interaction and the following intricate signal accident.

关 键 词：可诱导共刺激分子 成熟树突状细胞 反向信号 TGF-Β1 

分 类 号：R392.11[医药卫生—免疫学]