ICAM-1参与系统性红斑狼疮中免疫球蛋白产生的实验研究  被引量:4

Experimental study of ICAM-1 involvement in immunoglobulin production in systemic lupus erythematosus

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作  者:李玉梅[1,2] 刘帅 刘芝翠 王树军 季萍[1,2] 潘萌 张美玉[1,2] 王颖 LI Yu-Mei;LIU Shuai;LIU Zhi-Cui;WANG Shu-Jun;JI Ping;PAN Meng;ZHANG Mei-Yu;WANG Ying(Department of Blood Transfusion,Shanghai Ninth People Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 201999,China)

机构地区:[1]上海交通大学医学院附属第九人民医院输血科,上海201999 [2]上海交通大学医学院,上海200025 [3]上海交通大学医学院附属瑞金医院,上海200025

出  处:《中国免疫学杂志》2020年第11期1358-1364,共7页Chinese Journal of Immunology

基  金:国家自然科学基金面上项目(31170828和31370884)资助。

摘  要:目的:探讨ICAM-1在系统性红斑狼疮(SLE)免疫球蛋白产生中的作用。方法:流式细胞术检测分析SLE患者、健康者、anti-CD3 Ab/IFN-α刺激健康者CD4^+T细胞及Pristane诱导的狼疮样小鼠及对照鼠中CD4^+T细胞的活化表型;分选获得Pristane处理小鼠来源的CD4^+T细胞和B细胞,并于体外交叉共培养,加入ICAM-1阻断抗体或同型对照抗体,ELISA检测培养上清中IgG和IgM水平。结果:SLE患者及anti-CD3 Ab/IFN-α刺激健康者CD4^+T细胞表达HLA-DR,CD69和ICOS等分子的细胞比例明显高于对照组。Pristane诱导的狼疮样小鼠CD4^+T细胞的活化程度也显著高于对照;Pristane诱导的狼疮样小鼠血清中抗snRNP和抗dsDNA自身抗体水平显著高于对照组;Pristane处理小鼠来源的活化CD4^+T细胞与B细胞共培养可以促进B细胞产生IgM和IgG。而经抗ICAM-1抗体阻断处理的培养上清中IgM含量低于对照组,而IgG含量显著高于对照组。结论:Pristane来源的活化CD4^+T细胞可促进B细胞分化,ICAM-1分子可能在B细胞分化早期发挥作用,但不利于IgM型向IgG型的类别转换,为ICAM-1在SLE中抗体类别转化的分子机制提供新的理论依据。Objective:To investigate role of ICAM-1 in immunoglobulin production in systemic lupus erythematosus(SLE).Methods:Activation of CD4^+T cells in SLE patients,healthy donors stimulated by anti-CD3 Ab/IFN-α,as well as those from pristane-induced lupus like mice were analyzed by flow cytometry.CD4^+T cells and B cells from either pristane or PBS treated mice were co-cultured with or without anti-ICAM-1 neutralizing antibody in vitro.Total IgM and IgG levels in culture of supernatants were detected by ELISA.Results:Expression levels of HLA-DR,CD69 and ICOS on CD4^+T cells from SLE patients or anti-CD3 Ab/IFN-αstimulated CD4^+T cells from healthy donors were significantly higher than those from control.CD4^+T cells in spleens of pristane-induced lupus-like mice exhibited similar activated phenotype as well when compared to control.Levels of anti-snRNP and anti-dsDNA autoantibodies in serum of pristane-induced lupus-like mice were significantly higher than those in control.Total IgG and IgM amounts increased when pristane-derived CD4^+T cells were co-cultured with B cells either from PBS or pristane-treated mice.More interestingly,IgG level increased while IgM level decreased in culture supernatants of CD4^+T-B cell co-culture treated with anti-ICAM-1 Ab as compared to isotype Ab control.Conclusion:Activated CD4^+T cells from pristane can promote differentiation of B cells,and ICAM-1 is engaged in CD4^+T-B cell interaction at early stage of B cell differentiation whereas not conducive to IgM-to-IgG switch,which provides novel theoretical basis on molecular mechanism of ICAM-1 involved in antibody production during SLE.

关 键 词:系统性红斑狼疮 CD4^+T细胞 Pristane诱导狼疮样小鼠模型 IgG/IgM产生 ICAM-1 

分 类 号:R392[医药卫生—免疫学]

 

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