CD4＋T细胞亚群失衡与溃疡性结肠炎发病的关系  

Imbalance of CD4＋T cell subgroups in ulcerative colitis

作　　者：晁康[1] 钟碧慧[1] 张盛洪[1] 龚晓蓉[1] 姚佳燕[1] 陈旻湖[1] 

机构地区：[1]中山大学附属第一医院消化内科,广州510080

出　　处：《中华医学杂志》2011年第23期1605-1608,共4页National Medical Journal of China

基　　金：广东省科技计划项目（2009B030801174）

摘　　要：目的 探讨CD4＋T细胞亚群间的免疫紊乱与溃疡性结肠炎（UC）发病的关系.方法 收集24例UC患者（缓解期5例,活动期19例）及17名健康志愿者的外周血标本,分别作为病例组及对照组,提取外周血单个核细胞并采用流式细胞术检测CD4＋T细胞各亚群的比例、采用荧光定量PCR检测各亚群相对应转录因子mRNA的表达,采用流式细胞微球技术（CBA）及酶联免疫吸附法（ELISA）检测各亚群主要细胞因子的蛋白表达水平.结果 （1） 病例组Treg细胞比例低于对照组（6.7%±1.7%比7.9%±1.4%,P=0.016）,尤其是活动期为著（6.4%±1.7%,P=0.005）,Treg细胞主要转录因子FOXP3 mRNA的表达低于对照组（P=0.020）,其主要细胞因子转化生长因子（TGF）-β1在血清中的浓度亦低于对照组[（21±8） μg/L比（28±7） μg/L,P=0.026].（2） 病例组Th1细胞数目、其主要转录因子mRNA表达及主要细胞因子的蛋白水平均与对照组差异无统计学意义.（3）病例组Th2细胞比例高于对照组（2.7%±1.1%比1.6%±0.4%,P=0.002）,尤其是活动期为著（2.8%±1.0%,P=0.001）,Th2细胞主要转录因子GATA-3 mRNA的表达是对照组的4.4倍（P=0.045）.（4）病例组Th17细胞比例高于对照组（3.4%±1.8% 比1.8%±0.7%,P=0.005）,Th17细胞主要转录因子RORγt mRNA的表达约是对照组的13倍 （P=0.001）; 其主要细胞因子IL-6和IL-17的表达亦均高于对照组 （均P〈0.05）.（5）病例组Treg/Th2和Treg/Th17均显著低于对照组且和活动度有关 （均P〈0.05）.结论 Treg、Th2和Th17细胞亚群间免疫失衡共同参与UC发病,可能是UC治疗新靶点.Objective To investigate the relationship of the imbalance of CD4＋T cell subgroups and the pathogenesis of ulcerative colitis （UC）.Methods Peripheral blood samples were collected from 24 UC patients and 17 healthy donors.Then the phenotype of CD4＋T cells and the major transcription factor expression of each subset were analyzed by flow cytometry and real-time PCR （polymerase chain reaction） respectively.The serum concentrations of major cytokines of each subgroup were measured by cytometric bead array （CBA） and ELISA （enzyme-linked immunosorbent assay）.Results （1） The proportion of Treg cells in the UC group was lower than the control group （6.7%±1.7% vs 7.9%±1.4%, P=0.016）, especially in active stage （6.4%±1.7%, P=0.005）. As compared with the control group, the expression of FOXP3 mRNA was lower in the UC Group （P=0.020）. And so was the serum concentration of TGF-β1 [（21±8） μg/L vs （28±7） μg/L, P=0.026].（2）There were no significant differences in Th1-related transcription factors and cytokines between two groups.（3） Th2 cells were higher in the UC group （2.7%±1.1% vs 1.6%±0.4%, P=0.002）, especially in active stage （2.8%±1.0%, P=0.001）.The expression of GATA-3 mRNA was 4.4 folds higher than that of the controls （P=0.045）.（4） Th17 cells were higher in the UC group （3.4%±1.8% vs 1.8%±0.7%, P=0.005）. And the RORγt mRNA expression was 13 folds higher in UC group （P=0.001）; the serum concentrations of IL-6 and IL-17 were higher in the UC group （both P〈0.05）. （5） The ratios of Treg/Th2 and Treg/Th17 were significantly lower in the UC group and associated with disease activity （both P〈0.05）.Conclusion The imbalances of Th2, Treg and Th17 subgroups may play pivotal roles in the pathogenesis of UC.

关 键 词：结肠炎 溃疡性 CD4阳性T淋巴细胞 免疫 

分 类 号：R574.62[医药卫生—消化系统]