2型糖尿病患者抗原特异性T细胞功能研究及其临床意义  

Investigation on antigen-specific T cell responses in type 2 diabetes mellitus patients

作　　者：张一帆 黄艳红 Asma Khanniche 陈颖盈[2] 王树军[2] 季萍[2] 马小燕 王颖[2] 董艳 Zhang Yifan, Huang Yanhong, Asma Khanniche, Chen Yingying, Wang Shujun, Ji Ping, Ma Xiaoyan, Wang Ying, Dong Yan(Shanghai Institute for Pediatric Research, Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China)

机构地区：[1]上海市儿科医学研究所上海交通大学医学院附属新华医院内分泌科,200025 [2]上海市免疫学研究所

出　　处：《中华内分泌代谢杂志》2018年第9期761-767,共7页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的 研究2型糖尿病患者抗原特异性T细胞免疫功能特征及其对疾病的影响.方法 收集2016年8月至2017年5月于上海交通大学医学院附属新华医院内分泌科住院的2型糖尿病患者38例,以及健康体检者47名（对照组）的外周血样本,运用流式细胞技术检测2组研究对象CD4＋和CD8＋T细胞所占比例,测定佛波酯/离子霉素（PMA/Iono）刺激下外周血分泌干扰素（IFN）-γ、白细胞介素2（ IL-2）和肿瘤坏死因子（TNF）-α 的 CD4＋和 CD8＋T 细胞百分比,以及 EB 病毒抗原肽刺激下分泌 IFN-γ、IL-2和TNF-α的抗原特异性 CD8＋T 淋巴细胞百分比.结果 2 型糖尿病患者外周血 CD4＋T 细胞所占比例和CD4＋/CD8＋均明显高于对照组（P＜0.05）,而CD8＋T细胞比例在2组之间的差异无统计学意义;非特异性PMA/Iono刺激后,2型糖尿病患者外周血CD4＋和CD8＋T细胞中分泌IFN-γ、IL-2和TNF-α的细胞百分比与对照组相比均显著降低（P＜0.05）;而EB病毒抗原肽刺激后,2型糖尿病患者外周血分泌IFN-γ、IL-2和TNF-α的CD8＋T细胞百分比则显著高于对照组（P＜0.05）,且分泌TNF-α的细胞比例与HbA1C呈显著正相关（P＜0.05）.结论 2型糖尿病患者CD4＋和CD8＋T细胞分泌能力降低,但抗原特异性免疫应答则处于异常激活状态,提示慢性高血糖可损伤部分T细胞功能,加重慢性炎症.Objective To investigate the antigen-specific T cell functionality in type 2 diabetes mellitus patients. Methods Peripheral blood from 38 type 2 diabetes mellitus patients and 47 health controls （control group） have been collected. The proportions of CD4＋and CD8＋T cell as well as the ratio of CD4＋/CD8＋were monitored by flow cytometry. Meanwhile, antigen- nonspecific and specific Th1 responses were compared between two groups through detecting interferon （IFN）-γ, interleukin 2 （IL-2）, and tumor necrosis factor （TNF）-α producing cells upon propylene glycol monomethyl ether acetate （PMA）/ionomycine and epstein-barr virus （ EBV） peptides stimulation, respectively followed by an intracellular cytokine staining. Results Compared to control group, the proportion of CD4＋T cell and the ratio of CD4＋/CD8＋were significantly increased in type 2 diabetes mellitus group （P＜0.05） whereas CD8＋T cells exhibited no significant difference between two groups. Antigen-nonspecific Th1 responses in type 2 diabetes mellitus patients were significantly decreased, demonstrated by lower percentages of IFN-γ, IL-2, and TNF-α producing CD4＋T cells when compared to control group , while CD8＋T cells in type 2 diabetes mellitus patients exhibited similar cytokine production patterns. However, when stimulated by EBV specific peptides, the percentages of IFN-γ, IL-2, and TNF-α producing CD8＋T cells were significantly higher in type 2 diabetes mellitus patients than those in control group （P＜0.05）. HbA1Cwas positively correlated with the percentage of EBV-specific TNF-α producing CD8＋T cells （P＜0.05）. Conclusion In type 2 diabetes mellitus, the secretion capacity of CD4＋and CD8＋T cell was significantly decreased and the antigen-specific responses represent the presence of an abnormal activated status, which indicates that chronic hyperglycemia may damage T cells function and aggravate chronic inflammation.

关 键 词：糖尿病 2型 抗原特异性T细胞应答 CD4^+T细胞 CD8^+T细胞 细胞因子 

分 类 号：R587.1[医药卫生—内分泌]