Bcl-2家族蛋白参与调节CD3ε和5-氟尿嘧啶介导的T淋巴细胞凋亡  

Bcl-2 family proteins regulate T lymphocyte apoptosis mediated by CD3ε and 5-FU

作　　者：程宏[1] 刘彦信[1] 张锦春[1] 刘士廉[1] 郑德先[1] 

机构地区：[1]中国医学科学院基础医学研究所中国协和医科大学基础医学院医学分子生物学国家重点实验室,北京100005

出　　处：《中国免疫学杂志》2005年第1期17-21,共5页Chinese Journal of Immunology

基　　金：国家重大基础性研究 (973 )项目 (No G2 0 0 0 0 5 70 0 7);国家自然科学基金 (No 3 0 170 3 62 )资助

摘　　要：目的 :研究Bcl 2家族成员在 5 氟尿嘧啶 (5 FU)和CD3ε介导的T淋巴细胞凋亡中的作用 ,阐述T淋巴细胞凋亡的分子机制 ,为相关肿瘤的治疗提供依据。方法 :用CD3ε特异的单克隆抗体 (2 0 0 μg/ml)和 5 FU(2 5 μg/ml)单独或联合刺激JK、TJK和T3JK细胞 ,诱导细胞凋亡 ,用MTS比色法检测细胞死亡率 ,用Westernblot检测Bid的表达和活化。用脂质体的方法转染细胞。结果 :CD3ε特异的单克隆抗体和 5 FU分别单独处理TJK细胞 ,都能诱导其凋亡并伴随Bid的活化 ,二者联合使用能显著增加TJK细胞凋亡和Bid的活化。Bcl 2过表达可明显降低TJK细胞对 5 FU的敏感性。结论 :Bcl 2家族成员参与CD3ε和 5 FU诱导的T淋巴细胞凋亡的调节 ,Bcl 2过表达能显著抑制T淋巴细胞对 5 FU的敏感性。Objective:To investigate the regulation of Bcl 2 family on T lymphocyte apoptosis mediated by CD3ε and/or 5 FU (5 fluorouracil) and to provide a novel insight of the apoptosis signaling pathway and the implication for the clinic therapy of T lymphocyte leukemia.Methods:JK,TJK and T3JK cells stimulated with anti CD8 mAb (200 μg/ml) cross link and/or 5 FU (2 5 μg/ml) for 34 h.MTS assay was used to detect cell viability.Bcl 2 and Bid activation and expression were detcted by Western blot.Bcl 2 expression plasmid was stably transfected into TJK cells by electroporation method (250 μF,300 Volts).Results:Bid was activated in the TJK apoptosis induced by CD3ε specific monoclonal antibody or 5 FU.The apoptosis rate and Bid activation increased remarkably in the TJK cells cotreated with the CD3ε specific monoclonal antibody and 5 FU.Bcl 2 overexpression in the TJK cells decreased the sensitivity to 5 FU and maintained cell cycle.Conclusion:Bid plays an important role in the regulation of T lymphocyte apoptosis and is localized at the cross point of the two signaling pathway mediated by CD3ε and 5 FU,respectively. [

关 键 词：CD3ε 5-FU BID Bcl-2 细胞凋亡 

分 类 号：R392.12[医药卫生—免疫学]