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Induction of apoptosis of peripheral activated T lymphocytes by immunosuppressants
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 11
- DOI:
- 10.3760/cma.j.issn.0254-1785.2006.11.001
- Key Word:
- 细胞凋亡;免疫抑制剂;T淋巴细胞
Abstract： 目的 探讨各种免疫抑制剂在体外对人外周血淋巴细胞凋亡的诱导作用及其机制.方法 从健康人外周血中分离T淋巴细胞,经抗原刺激诱导淋巴细胞活化,将霉酚酸酯(MMF)、环孢素A(CsA)、他克莫司(FK506)、西罗莫司、泼尼松(Pred)、达利珠单抗及硫唑嘌呤(Aza)单独或联合加入静止T淋巴细胞和活化T淋巴细胞中共同培养,3 d后,采用共聚焦显微镜、流式细胞仪、DNA片段化电泳分析及逆转录聚合酶链反应基因扩增方法检测淋巴细胞凋亡发生率,酶联免疫吸附试验检测试剂盒测定细胞培养基中白细胞介素2(IL-2)和Fas的表达水平.结果 各种免疫抑制剂中,仅Pred能明显促进静止T淋巴细胞凋亡.MMF、Aza及Pred均能促使活化T淋巴细胞发生凋亡(P＜0.05,P＜0.01),而CsA、FK506、西罗莫司及达利珠单抗均抑制活化T淋巴细胞的凋亡(P＜0.01).两种或三种不同的免疫抑制剂同时加入活化T淋巴细胞的培养基中,其凋亡细胞明显少于对照组(P＜0.01).FK506和CsA能显著抑制活化T淋巴细胞的Fas和IL-2表达(P＜0.05).结论 MMF、Aza及Pred可能通过Fas/FasL信号通路诱导活化T淋巴细胞的凋亡,而CsA和FK506通过抑制IL-2的产生而阻碍活化T淋巴细胞的凋亡,西罗莫司和达利珠单抗则可能通过阻断IL-2的活化效应而抑制活化T淋巴细胞的凋亡.
- [1]A K, Abbas.Die and let live: eliminating dangerous lymphocytes.[J].1996,84(5).
- [2]Droin N,Green DR,Pinkoski M.Activation-induced cell death in T cells.[J].2003,193(0).
- [3]Walsh PT,Turka L,Chiffoleau E.Apoptosis and transplantation tolerance.[J].2003,193(0).
- [4]Douillard P,Cuturi MC,Gilbert E,etc.Fas ligand, tumor necrosis factor-alpha expression, and apoptosis during allograft rejection and tolerance.[J].1998,66(7).
- [5]Li Y,Hancock WW,Turka LA,etc.Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance.[J].1999,5(11).
- [6]Ferguson TA,Griffith TS,Herndon JM,etc.Apoptosis, tolerance, and regulatory T cells--old wine, new wineskins.[J].2003,193(0).
- [7]Woodside KJ,Meng T,Hu M,etc.Differential effects of interleukin-2 blockade on apoptosis in naive and activated human lymphocytes.[J].2003,75(10).
- [8]X C, Li,A D, Wells,T B, Strom,etc.The role of T cell apoptosis in transplantation tolerance.[J].2000,12(5).