不同时期应用抗L3T4单抗治疗的自身免疫性心肌病小鼠免疫球蛋白G亚型分析  

Analysis of IgG subsets in mice with experimental cardiomyopathy after treating with anti-L3T4 monoclonal antibody in different stages

作　　者：汪朝晖[1] 袁璟[1] 王敏[1] 张景辉[2] 田元[2] 董继华[3] 刘仲平[4] 廖玉华[1] 

机构地区：[1]华中科技大学协和医院心内科华中科技大学心血管病研究所,武汉430022 [2]华中科技大学协和医院普外科实验室,武汉430022 [3]华中科技大学协和医院病毒学实验室,武汉430022 [4]华中科技大学协和医院血液病研究所,武汉430022

出　　处：《临床心血管病杂志》2007年第7期498-501,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助项目(No:30000070)

摘　　要：目的:探讨不同阶段应用抗L3T4单抗治疗自身免疫性心肌病对小鼠血清抗线粒体ADP/ATP载体抗体和免疫球蛋白G(IgG)亚型的影响。方法:将24只小鼠随机分为4组,每组6只。用含有人线粒体ADP/ATP载体肽的免疫液免疫近交系Balb/C小鼠建立类扩张型心肌病(DCM)模型(DCM组);以不含肽免疫液免疫小鼠作为对照组;在同时用含有ADP/ATP载体肽的免疫液的第0、1、2天连续3d以400μg抗L3T4单抗免疫小鼠获得早期治疗组;在给予ADP/ATP载体肽的免疫液第4个月初始连续3d给予抗L3T4单抗治疗获得中期治疗组。以ELISA法检测其血清中抗ADP/ATP载体抗体水平和IgG亚型(IgG1、IgG2a、IgG2b和IgG3)的变化;采用流式细胞术检测小鼠脾脏中CD4+T细胞内γ干扰素(IFN-γ)/白细胞介素(IL)-4的表达。结果:早期治疗组与对照组小鼠抗ADP/ATP载体抗体检测均为阴性,而中期治疗组与DCM组抗体均为阳性。DCM组各亚类水平均较对照组明显升高;早期治疗组IgG1、IgG2b和IgG3的产生均受到抑制,其水平接近对照组;中期治疗组IgG1水平介于DCM组和早期治疗组之间,IgG2b和IgG3的生成与DCM组差异无统计学意义,但显著高于早期治疗组;而治疗组与DCM组IgG2a水平则差异无统计学意义。早期治疗组小鼠IFN-γ/IL-4百分含量与对照组相比差异无统计学意义,但明显低于DCM组;中期治疗组IFN-γ的百分含量较DCM组更高,IL-4的百分含量介于DCM组和早期治疗组之间。结论:抗L3T4单抗治疗能够抑制DCM小鼠血清中的抗ADP/ATP载体抗体及IgG1亚型的生成和Th2相关细胞因子IL-4的百分含量,且以早期治疗的效果更明显。Objective： To explore the IgG subsets in mice with experimental cardiomyopathy treated by anti- L3T4 monoclonal antibody （McAb） in different stages. Method： Mice immunized with the human mitochondria ADP/ATP peptides were used as cardiomyopathy （DCM） group, and the sham-immunized mice were regarded as the controls. Mice in the early-treated group were immunized with the same peptides, followed by tail vein injectin of 400 μg anti-L3T4 monoclonal antibody on day 0, 1 and 2 post-immunization. Mice in the late-treated group were immunized as early-treated group but administered of anti-L3T4 after 3 months. Serum anti-ADP/ATP carrier antibody and IgG subsets （IgG1, IgG2a, IgG2b, IgG3） were measured by enzyme-linked immunosorbent assay （ELISA） and the percentages of interferon （IFN-γ） and interleukin-4 （IL-4） producing cells in splenic CD4-positire lymphocytes were using flow cytometry analysis. Result： Serum antibodies against the ADP/ATP carrier in early-treated group were detected negative as those in controls, while positive in the late-treated and DCM groups. All the IgG subsets in DCM group increased as compared to the controls, whereas the production of IgG1, IgG2b and IgG3 in early-treated group was significantly reduced. IgG1 level in late-treated group was higher than in the early-treated group and lower than in the DCM group. Both IgG2b and IgG3 levels in late-treated group were similar to the DCM group＇s levels but higher than in the early-treated group. As to IgG2a levels, they didn＇t show significant difference within the DCM group and anti L3T4 treated groups. The percentages of T cell cytokine IFN-γ and IL-4 in the early-treated group was similar to the controls but significantly reduced compared to the DCM group, while in the late-treated group the IFN-γ level was higher than in the DCM group and IL-4 level was higher than in the early-treated group and lower than in the DCM group. Conclusion： anti-L3T4 McAb could inhibit the production of anti-ADP/ATP carrier a

关 键 词：心肌病 扩张型 自身免疫 免疫治疗 免疫球蛋白G 细胞因子 

分 类 号：R542.2[医药卫生—心血管疾病]