骨髓增生异常综合征小鼠滤泡辅助T细胞及表面分子PD-1表达的研究  

Follicular Helper T Cells and Expression of PD-1 in Mice with Myelodysplastic Syndrome

作　　者：崔宁博[1] 王化泉[1] 李德冠[2] 闫玉军[2] 孟爱民[2] 邵宗鸿[1] 

机构地区：[1]天津医科大学总医院血液科,天津300052 [2]中国医学科学院放射医学研究所,天津300192

出　　处：《中国实验血液学杂志》2015年第3期756-760,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(81170472;81400088);天津市应用基础与前沿技术研究计划(14JCYBJC27200;09JCYBJC11200);天津市"抗癌重大专项攻关计划"项目(12ZCDZSY17900)

摘　　要：目的:观察骨髓增生异常综合征(MDS)小鼠血象和骨髓象变化、骨髓和脾脏滤泡辅助T细胞(Tfh)数量及表面分子程序化死亡分子-1(PD-1)的表达情况,探讨其在MDS发病机制中的作用。方法:分别选取10只雄性NUP98-HOXD13转基因小鼠及其同源的野生型C57BL/6J小鼠作为实验对象,行外周血细胞计数,瑞氏染色观察外周血细胞变化、骨髓细胞涂片检查细胞形态;流式细胞术检测骨髓单个核细胞(BMMNC)及脾脏来源的Tfh细胞数量及其表面分子PD-1表达;实时定量PCR法分析BMMNC及脾脏来源细胞PD-1 mRNA的表达。结果:上述转基因小鼠的红细胞、中性粒细胞和血小板数均低于野生型C57BL/6J小鼠;与野生型C57BL/6J小鼠比较,转基因小鼠外周血红细胞及血小板形态相对大小不均,骨髓中可见双核红细胞、环状核粒细胞和红系造血岛等;转基因小鼠骨髓及脾脏Tfh数量较野生型小鼠少,且表面分子PD-1表达率增高;还发现该小鼠BMMNC PD-1 mRNA表达量明显高于野生型小鼠。结论:NUP98-HOXD13转基因小鼠出现全血细胞减少和病态造血,Tfh数量减少,PD-1表达量升高,可能是导致机体免疫功能抑制,促进恶性克隆逃逸免疫监视的重要原因之一。Objective：To investigate the complete blood count, morphological changes, follicular T helper （Tfh） cells and expression of PD-1 in bone marrow and spleen of mice with myelodysplastic syndrome（ MDS ） and to explore their significance in pathogenesis of MDS. Methods： The 10 male NUP98-HOXD13 transgenic mice and 10 male homologous wild-type C57BL/6J mice were used for experments. The complete blood count, morphological change of NUP98-HOXD13 transgenic mice and wild-type C57BL/6J were detected by routine methods. The level of Tfh cells and expression of PD-1 in bone marrow and spleen were measured by flow cytometry. The PD-1 mRNA of bone marrow mononuclear cells and spleen cells were analyzed by real-time PCR method. Results：The counts of RBC, neutrophile and platelet in abovementioned transgenic mice were less than that in wild type C57BL/6J mice. As compared with wild type C57BL/6J mice, the morphology of RBC and platelet in transgenic mice was some abnormal, including bi- nucleated erythrocytes, ringed mucleated neutrophil and erythroblastic islands. The count of Tfh cells in transgenic mice was less than that in wild type mice, but the expression of PD-1 was higher. The expression of BMMNC PD-1 mRNA was obviously higher than that in wild type mice. Conclusion：The pancytopenia and dysplasia, decrease of Tfh cells and increase of PD-1 expression have been observed in NUP98-HOXD13 transgenic mice, which may be one of important reasons for promoting malignant clone and leading to impair anti immune respones.

关 键 词：骨髓增生异常综合征 滤泡辅助T细胞 程序化死亡受体1 

分 类 号：R551.3[医药卫生—血液循环系统疾病]