共刺激分子B7-H4对干燥综合征模型NOD鼠T细胞亚群的作用  

Effect of costimulatory molecules B7-H4 on T lymphocyte subsets of NOD mice in Sjgren's syndrome

作　　者：王其凯 袁祥 周滢波 郑旭 王雪 李向培 汪国生 王怡平 厉小梅 WANG Qi-kai, YUAN Xiang, ZHOU Ying-bo, ZHENG Xu,WANG Xue, LI Xiang-pei, WANG Guo-sheng, WANG Yi-ping, LI Xiao-mei(Department of Rheumatology and Immunology, the Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, Chin)

机构地区：[1]安徽医科大学附属省立医院风湿免疫科,安徽合肥230001

出　　处：《中华疾病控制杂志》2018年第7期731-735,共5页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81373187)

摘　　要：目的探讨共刺激分子B7-H4对干燥综合征(Sjgren's syndrome,SS)模型非肥胖型糖尿病(nonobese diabetic,NOD)鼠T细胞亚群的调节作用。方法将雌性NOD鼠随机分为基线组5只、生理盐水(normal saline,NS)组5只、B7-H4-Fc蛋白组8只、Ig G2a-Fc组6只。在0 d和30 d时,将小鼠麻醉后处死,并取脾脏和颌下腺;流式细胞术检测脾脏单细胞悬液中淋巴细胞亚群的变化,颌下腺组织做苏木精和伊红染色和免疫组织化学染色。结果共刺激分子B7-H4蛋白主要表达于NOD鼠颌下腺导管内皮细胞胞浆,组织病理显示颌下腺中有大量淋巴细胞浸润时B7-H4蛋白低表达。腹腔注射B7-H4-Fc融合蛋白30 d后NOD鼠颌下腺炎症浸润程度减轻。B7-H4-Fc组分别与Ig G2a-Fc组、NS组、基线组比较时,脾脏中的CD4+Foxp3+T细胞/CD4+T细胞百分比升高,差异均有统计学意义(均有P<0.05);而B7-H4-Fc组较Ig G2a-Fc组、NS组、基线组CD4+IFN-γ+T细胞/CD4+T细胞百分比均降低(均有P<0.05);三组间脾脏中CD4+IL-17+T细胞/CD4+T细胞百分比差异无统计学意义(均有P>0.05)。结论 B7-H4蛋白可延缓NOD小鼠颌下腺淋巴细胞浸润,减轻体内炎症细胞因子水平,抑制自身免疫炎症的进展。Objective To investigate the effect of co-stimulatory molecule B7-H4 on the regulation of T cell subsets in non--obese diabetic（NOD） mice induced by SjOgren＇s syndrome （SS）. Methods Female NOD mice were randomly divided into baseline group, normal saline （NS） group, BT-H4-Fc protein group, IgG2a-Fc group. After 0 days and 30 days, The mice were sacrificed after being anesthetized, and the spleen and submandibular glands were taken out. The changes of lymphocyte subsets in spleen single cell suspension were detected by flow cytometry, and the submandibular gland tissue was stained with HE and immunohistoehemistry. Results Costimulatory molecule B7-H4 protein was mainly expressed in cytoplasm of submandibular gland ductal endothelial cells in NOD mice. A low expression of B7-H4 protein was found in a large number of lymphecytes infiltrated in the submandibular gland. The degree of inflammatory infiltration of submandibular gland in NOD mice was significantly reduced after intraperitoneal injection of B7-H4-Fc fusion protein at day 30. The percentages of CD4＋Foxp3＋Tcell/CIM＋Tcell in spleen were significantly increased in BT-H4-Fc group compared with IgG2a-Fc group, NS group and baseline group respectively （ all P〈0. 05）. The percent- age of CD4＋IFN-γ＋Tcell/CD4＋Tcell in BT-H4-Fc group was significantly lower than that in IgG2a-Fc group, NS group and baseline group （all P〈0.05）. There was no significant difference in the proportion of CD4＋IFN-γ＋T cells in the spleen between the three groups in the proportion of CIM＋T cells. Conclusions B7-H4 protein can delay the infiltration of lymphocyte in the submandibular gland of NOD mice, reduce the level of inflammatory eytokines and inhibit the progress of autoimmune inflammation.

关 键 词：B7-H4 干燥综合征 共刺激分子 自身免疫性疾病 NOD鼠 

分 类 号：R593.2[医药卫生—内科学]