T-bet重组腺病毒对哮喘小鼠Thl/Th2免疫平衡的调节  

Regulation of recombinant T-bet adenovirus on Thl/Th2 balance in mouse model of asthma

作　　者：陈吉泉[1] 修清玉[1] 何皓頔[1] 刘涛[1] 颜泽敏[1] 

机构地区：[1]第二军医大学长征医院呼吸内科,上海200003

出　　处：《免疫学杂志》2007年第1期58-61,共4页Immunological Journal

基　　金：国家自然科学基金项目资助(30200116)

摘　　要：目的探讨静脉应用T-bet重组腺病毒(AdT-bet)对哮喘模型小鼠过敏性气道炎症及Th1/Th2免疫失衡的影响。方法36只C57BL/6小鼠随机分为AdT-bet治疗组(A组)、模型对照组(B组)、正常组(C组)。以卵蛋白(OVA)、氢氧化铝免疫建立哮喘模型,A组激发前尾静脉注射100μL的AdT-bet(1×108PFU/μL),各组激发后肺泡灌洗分析细胞组份,分离肺淋巴细胞测定细胞因子分泌水平,以流式细胞仪检测CD3+、CD4+T细胞比例及表达IFNγ和IL-4的比例,比较各组肺组织学改变。结果静脉应用AdT-bet组与对照组相比①可明显抑制抗原激发后气道内嗜酸性粒细胞的浸润(P<0.01);②明显抑制肺淋巴细胞产生IL-4、IL-5,增加了IFNγ的产生;③肺脏淋巴细胞CD4+IFNγ+百分比及IFNγ+/IL-4+明显升高(P<0.01),而CD4+IL-4+百分比则明显下降;④明显抑制哮喘鼠气道内及肺泡内的过敏性炎症反应。结论激发前静脉用AdT-bet对哮喘小鼠过敏性气道炎症有明显的防治作用,其机制可能与表达的T-bet上调Thl/Th2比值,从而调整了免疫平衡有关。Objective To investigate the effect of recombinant T-bet adenovirus （AdT-bet） on the antigen-induced allergic airway reaction and Th1/Th2 imbalance in mice with asthma. Methods Thirty-six C57BL/6 mice were randomly divided into AdT-bet treated group （group A）, PBS control group （group B）, and normal group （group C）. The asthma model was established in C57BL/6 mice by immunization with OVA and Al（OH）3. Recombinant T-bet adenovirus was administrated intravenously in tail vein at the dose of 10^8 PFU/100μL. The cellular composition of bronchoalveolar lavage fluid was analyzed after challenge in every group. The lung lymphecytes were isolated for cytokines secretion detection and FCM analysis of intracellular IFNγ/and IL-4 positive CD3^＋ and CD4 ^＋ T cells. The histological changes in the lung were compared in every group. Results Compared with control group, intravenous administration of recombinant T-bet adenovirus markedly inhibited the eosinophilia in the lung, inhibited the IL-4 and IL-5 production from isolated lung T cells, and enhanced the IFNγ/production from these cells simultaneously. The percentage of CD4^＋ IFNγ lung lymphecytes and the ratio of IFNγ^＋ to IL-4^＋ lung T cells were enhanced significantly but the percentage of CD4^＋ IL-4^＋ lung T cells were decreased in AdT-bet-treated group. The intravenous administration of recombinant T-bet adenovirus inhibited the allergic inflammation in the airway and the lung tissue. Conclusion Intravenous administration of recombinant T-bet adenoviras can inhibit the antigen-induced airway allergic reactions significantly, which involves up-regulation of Th1/Th2 ratio by expressing T- bet after gene delivery with recombinant adenovirus vector.

关 键 词：哮喘 T-bet重组腺病毒 TH1/TH2失衡 免疫调节 

分 类 号：R562.25[医药卫生—呼吸系统]