环孢菌素通过FLIP影响再生障碍性贫血患者CD8^+ T细胞亚群CD28的表达  

Cyclosporin A can affect the CD28 expression of CD8^+ T cells in patients with aplastic anemia via down-regulation of FLIP

作　　者：黄海雯[1] 吴德沛[1] 陈广华[1] 傅晋翔[2] 於葛华[3] 张学光[3] 

机构地区：[1]苏州大学附属第一医院血液科,215007 [2]苏州大学附属第二医院血液科 [3]苏州大学生物技术研究所

出　　处：《中华微生物学和免疫学杂志》2007年第10期900-903,共4页Chinese Journal of Microbiology and Immunology

摘　　要：目的研究共刺激分子CD28在再生障碍性贫血(AA)患者的不同T细胞亚群中的表达变化,及其与凋亡抑制蛋白FLIP的关系。方法取21例AA患者环孢菌素A(CyA)治疗前后的外周血,应用流式细胞仪检测T细胞CD4CD28、CD8CD28的表达;磁珠分选患者治疗前后外周血的CD8+ T细胞,RT-PCR检测治疗前后FLIP、Caspase-8表达变化;分选获得的治疗前的CD8+T细胞体外经CyA处理后检测其CD28、FLIP、Caspase-8的表达变化。结果AA患者的CD8+CD28-T细胞的比例较正常人显著升高,治疗有效者该亚群的细胞比例在治疗后趋于正常;患者CD8+T细胞的FLIP表达显著上调,但Caspase-8的表达无明显变化;CyA能下调患者CD8+T细胞的FLIP的表达。结论AA患者CD8+CD28- T细胞亚群比例升高与FLIP表达增加有关,CyA能抑制FLIP的表达,降低CD8+CD28- T细胞的比例。Objective To study the expression of CD28 on different subgroups of T cells in patients with aplastic anemia （AA） and the relationship with the expression of Fas-associated death domain-like 1L-lβ-converting enzyme inhibitory protein （FLIP）. Methods Twenty-one patients and 15 healthy controls were investigated. The expression of CIMCIY28 and CDSCD28 on patients＇ T cells was examined with flow cytometry （FCM）; patients＇ CD8^＋ T cells were purified with mini MARC system, then the expression of FLIP, Caspase-8 in CD8^＋ T cells were analyzed by RT-PCR; and the expression of CD28, FLIP and Caspase-8 in patients＇ CD8^＋ T cells cultured with cyclosporin A （CyA） was also examined. Results The percentage of CD8^＋ CD28^- T cells in the patients is significantly higher than that of normal controls （30.45% ± 5.26% versus 19.32% ± d. 72%, P 〈 0.05） and it can be induced to return to normal after effective treatment with CyA; the expression of FLIP in CD8^＋ T cells of AA patients is higher than that in healthy control CD8^＋ T cells, but there is no difference in the expression of Caspase-8; after being cultured with CyA, the expression of FLIP in patients＇ CD8^＋ T cells was down-regulated and the quantity of CD28 on the surface of patients＇ CD8^＋ T cells increased significantly. Conclusion The increased expression of FLIP in patients＇ CD8^＋ T cells is related to the increased percentage of CD8^＋ CD28^- T cells in patients＇ peripheral blood. CyA can down-regulate the FLIP expression and correct the abnormal percentage of CD8^＋ CD28^- T cells in ,atients with AA.

关 键 词：再生障碍性贫血 CD8^+CD28^- T细胞 FLIP 环孢菌素A 

分 类 号：R96[医药卫生—药理学] R556[医药卫生—药学]