天花粉蛋白及其肽段诱导的免疫抑制依赖APC表面Notch配体的表达  

Dependence on the expression of Notch ligands on APC for the immune suppression induced by Trichosanthin and a Trichosanthin-derived peptide

作　　者：焦志军[1] 周芸[1] 辛利军[1] 路丽明[1] 丁庆[1] 周晓荣[1] 杨能[1] 周光炎[1] 

机构地区：[1]上海交通大学医学院上海市免疫学研究所,上海200025

出　　处：《现代免疫学》2006年第6期448-453,共6页Current Immunology

基　　金：国家自然科学基金重点资助项目(30530690);上海市科委基金资助项目(05DZ19734)

摘　　要：新近发现,Notch信号途径参与调节外周成熟T细胞及其亚群的分化和功能发挥。本研究应用天花粉蛋白及其衍生肽处理骨髓来源的小鼠树突状细胞(DC),检测Notch配体家族分子的表达及DC对CD8+T细胞分泌细胞因子的影响。结果表明,天花粉蛋白或其衍生肽PB处理DC可使Notch配体Jagged1、Delta1分子表达明显增加,并改变CD8+T细胞细胞因子分泌格局,明显抑制Th1相关细胞因子IFN-γ的分泌,而Th2相关细胞因子IL-4和IL-10分泌明显增加。Notch信号的阻断剂可以部分逆转Tk及肽段的抑制作用。表明天花粉蛋白及其衍生肽可诱导一群具有抑制能力的CD8+T细胞,该作用依赖于DC表面Notch配体的表达。As demonstrated recently, Notch-initlated signaling is active in regulation of differentiation and functions of T cells and its subsets. In this study, mouse bone marrow derived dendritic cells （BM-DC） were treated with Trichosanthin and a related peptide to reveal the possible change of expression patterns of Notch ligands and the influences on cytokine secretion of CD8^＋ T cells. The results we obtained showed that in compared with the elevated expression of four Notch ligands, Jaggedl, Jagged2, Deltal and Delta 4, after treated with LPS alone, only two of them, Jaggedl and Deltal, demonstrated significantly and mildly increase of expression when BM-DC were treated with LPS＋Tk and LPS＋Tk-derived peptide, respectively. Tkor PB-treated DC showed a changed profile of cytokines produced by CD8^＋ T cells that were activated by anti-CD3 and CD28 mAb. Among them, IL-4 and IL-10 were up-regulated while IFN-γ was down-regulated. Adoptive transferring experiments demonstrated that the CD8＋ T cells could inhibit the antigen-specific lymphoproliferation. Blocking of the Notch-initiated signaling pathway by mAb DAPT partially recovered the suppression induced by Tk or PB peptide. This suggests that CD8^＋ T cell-mediated immune suppression induced by Tk and Tk derived-peptide was dependent on the expression of certain Notch ligands on antigen-presenting cells.

关 键 词：天花粉蛋白 Th2相关细胞因子 树突状细胞 NOTCH配体 

分 类 号：R392.11[医药卫生—免疫学]