NOD小鼠糖尿病早期Th1细胞与CD4^+CD25^+Treg细胞的变化  

Changes in Th1 cells and CD4^+CD25^+Treg cells in non-obese diabetic mice at early stage of diabetes

作　　者：王弘珺[1] 李质馨[1] 田洪艳[1] 徐冶[1] 刘忠平[1] 

机构地区：[1]吉林医药学院组织与胚胎学教研室,吉林省吉林市132013

出　　处：《解放军医学杂志》2013年第11期888-891,共4页Medical Journal of Chinese People's Liberation Army

基　　金：吉林省教育厅"十一五"科学技术研究项目(2008401);吉林省科技发展计划项目(20130101140JC)~~

摘　　要：目的研究Th1细胞和CD4+CD25+Treg细胞在NOD小鼠糖尿病早期的变化,并评价其作用。方法选择4周(A组)、8周(B组)和16周龄(C组)的雌性NOD小鼠,取脾、胸腺和胰腺组织,采用流式细胞术测定脾Th1和CD4+CD25+Treg细胞的比例,计算Th1/CD4+T、CD4+CD25+Treg/CD4+T和Th1/CD4+CD25+Treg的比值,再测定胸腺CD4–CD8–T、CD4+CD8+T、CD4–CD8+T和CD4+CD8–T细胞比例,计算CD25+Treg/CD4+CD8–T的比值。取胰腺组织,行HE染色和Foxp3免疫组化染色,观察胰腺病理学变化。结果 C组小鼠脾脏Th1细胞比例以及Th1/CD4+T和Th1/CD4+CD25+Treg比值明显高于A组和B组,但是A、B、C三组脾脏CD4+CD25+Treg细胞比例及CD4+CD25+Treg/CD4+T比值差异无统计学意义。三组间胸腺CD4–CD8–T、CD4+CD8+T、CD4–CD8+T和CD4+CD8–T细胞比例差异无统计学意义,但是B组和C组胸腺CD25+Treg/CD4+CD8–T比值明显高于A组。HE染色结果显示,B组和C组的胰岛周围可见淋巴细胞浸润,但胰岛周围淋巴细胞浸润部位免疫组化染色未见Foxp3阳性细胞。结论 NOD小鼠糖尿病早期外周Th1细胞呈进行性增加,但CD4+CD25+Treg细胞相对缺乏,考虑与NOD小鼠糖尿病进展有关。Objective To investigate the changes in Thl cells and CD4＋CD25＋Treg cells in non-obese diabetic （NOD） mice at early stage of diabetes, and to evaluate the significance of these changes. Methods Four week- （group A）, 8 week- （group B） and 16 week-old （group C） female NOD mice （8 each） were used in present study. The spleen, thymus and pancreas were harvested. Thl and CD4＋CD25＋Treg cells in spleen were determined by flow cytometer, and the ratios of Thl/CD4＋T, CD4＋CD25＋Treg/ CD4＋T and Th1/CD4＋CD25＋Treg were calculated. Subsequently, CD4-CDKT, CD4＋CD8＋T, CD4 CD8＋T and CD4＋CD8 T cells in thymus were determined by flow cytometer, and the ratio of CD25＋Treg/CD4＋CD8-T was calculated. The histopathological changes in pancreas were also evaluated by HE staining and immunohistochemistry staining. Results The proportion of Thl cells in spleen and the ratios of Thl/CD4＋T and Thl/CD4＋CD25＋Treg were higher significantly in group C than in group A and B. However, no significant differences were found in the proportion of spleen CD4＋CD25＋Treg cells and the ratio of CD4＋CD25＋Treg/CD4＋T among the three groups. Compared with group A, no obvious changes were found in thymus CD4 CD8-T, CD4＋CD8＋T, CD4 CD8＋T and CD4＋CD8 T cells in group B and C, but the ratio of thymus CD25＋Treg/CD4＋CD8-T increased significantly in group B and C. Lymphocytic infiltration was observed in pancreatic islets of group B and C as shown with HE staining, but Foxp3＋T cells were not seen in pancreatic islets by immunohistochemistry. Conclusion Thl cells are gradually increased at early stage of diabetes in NOD mice, but CD4＋CD25＋Treg cells are relatively default. These changes may play an important role in the progress of diabetes.

关 键 词：小鼠 近交NOD TH1细胞 CD4+CD25+调节性T细胞 糖尿病 1型 

分 类 号：R392.11[医药卫生—免疫学]