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转染IL-10的树突状细胞对小鼠哮喘气道表达的影响 被引量：3

The influence of the mouse recombinant adenovirus vector Ad-mIL-10 and its transfected dendritic cells on the airway inflammation in asthmatic mouse model
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摘要 研究小鼠重组腺病毒载体Ad-mIL-10及其转染的树突状细胞(dendritic cell,DC)对小鼠哮喘模型气道炎症的影响,探讨其相关的发病机制。用基因工程的方法构建小鼠IL-10腺病毒重组体Ad-mIL-10,并转染小鼠骨髓来源的DC。以卵白蛋白(OVA)腹腔注射致敏小鼠并雾化吸入激发的方法制作小鼠哮喘模型。第一次腹腔OVA致敏后静脉给予Ad-mIL-10、Ad-EGFP、Ad-EGFP转染的DC或Ad-mIL-10转染的DC,并设立哮喘模型制作对照组,观察各组小鼠血液、肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中的CD3+T细胞中的IL-10+IL-4-的Tr细胞及IL-10+IL-4+的Th2细胞比例变化,ELISA方法测定外周血及肺泡灌洗液中的IFN-γ、IL-4、IL-10水平,以观察Th1、Th2细胞的数量、功能变化以及IL-10的变化。结果显示Ad-mIL-10、Ad-EGFP、Ad-EGFP-DC对哮喘模型小鼠体内Tr细胞和Th2细胞的数量及肺部炎症局部的Th1及Th2细胞功能无明显影响;Ad-mIL-10转染的DC可以诱导哮喘模型小鼠体内IL-4-IL-10+的Tr细胞的增加及IL-4+IL-10+的Th2细胞的减少,并抑制哮喘模型小鼠肺部Th2细胞的功能,但对Th1细胞的功能无明显影响。提示单独应用Ad-mIL-10静脉注射产生高浓度的IL-10并不能诱导Tr细胞分化和抑制Th2细胞的激活。Ad-mIL-10转染的DC可以诱导原始T细胞向Tr细胞方向分化,并抑制Th2细胞的数量和功能。 To study the influence of the mouse recombinant adenovirus vector Ad-mIL-10 and its transfected dendritic cells （DCs） on the mouse airway inflammation in allergic asthma and to search for the related pathogenesis, this vector was constructed by using gene engineering methods and transfected to, DCs derived from bone marrow of mice. Mouse asthmatic model was established by intraperitoneal injection of ovalbumin（OVA） for sensitization and followed by OVA inhalation. Ad-mIL- 10 or the DCs transfected by Ad mIL-10 was adoptively transferred to mice after the first OVA intraperitoneal injection. The changes in the proportions of CD3＋ IL-10＋ IL-4- Tr cells and CD3＋ IL-10＋ IL-4＋ Th2 cells in blood and brochoalveolar lavage fluid（BALF） were observed by flow cytometry, and the levels of IFN 7, IL-4 and IL-10 were tested by ELISA to observe the quantity and function alterations of Thl and Th2 cells in asthma. The experimental results showed that no significant influence of Ad-mIL-10 on the quantity and function of Tr cells, Thl and Th2 cells in lungs of the mouse asthmatic model was ob- served, but it showed certain inhibitory effect on the function of blood Th2 cells. DC transfected by Ad-mIL 10 could induce the increase of IL-10＋ IL-4- Tr cells and the decrease of IL4＋ IL-10＋ Th2 cells and suppress the Th2 function of mouse asthmatic model, but have no impact on the Thl function. From these observations, it is evident that either Ad-mIL-10 or DC transfected by Ad-mlL-10 induce immunologic tolerance, but simple application of Ad-mIL-10 to produce high concentration of IL-10 is unable to induce the development of Tr cells and the suppression of Th2 cell activation. However, the Ad-mIL-10 transfected DCs can induce the naive T cells to differentiate into Tr cells, and suppress the quantity and function of Th2 cells.
作者 张伟 陈传辉 许飞 林耀广
机构地区 南昌大学第一附属医院呼吸内科
出处 《现代免疫学》 CAS CSCD 北大核心 2011年第1期60-65,共6页 Current Immunology
基金 "十一五"国家科技支撑计划资助项目(2008BAI68B00)
关键词 小鼠哮喘模型 免疫耐受 IL-10 树突状细胞 TR细胞 TH1细胞 Th2细胞. asthmatic mouse model immunologic tolerance interleukin 10 dendritic cells Tr cell Th1 ceil Th2 cell
分类号 R392-3 [医药卫生—免疫学]
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参考文献13

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共引文献14

同被引文献57

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现代免疫学
2011年 第1期

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