Defective CD3-mediated cell death in activated T cells from patients with systemic lupus erythematosus: Role of decreased intracellular TNF-alpha
Defective CD3-mediated cell death in activated T cells from patients with systemic lupus erythematosus: Role of decreased intracellular TNF-alpha
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DOI：
10.1006/clin.1996.0192
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发表时间：
1996-12-01
期刊：
影响因子：
--
通讯作者：
Tsokos, GC
中科院分区：
文献类型：
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作者：
Kovacs, B;Vassilopoulos, D;Tsokos, GC
激活诱导的细胞死亡(AICD)通过清除预先激活的和潜在的自身反应细胞，在免疫反应的调节中发挥重要作用。为了阐明人类系统性红斑狼疮(SLE)中AICD的可能异常，我们研究了SLE患者和正常对照激活的T细胞中的AICD。采用流式细胞术、碘化丙啶染色和DNA亚二倍体峰群分析等方法检测CD3介导的短期T细胞死亡。研究发现，SLE患者的T细胞比正常人的T细胞显著降低。抗Fas单抗诱导的细胞死亡在SLE细胞系和对照细胞系中相似。在对照和SLE T细胞系中，CD3介导的AICD可被抗Fas单抗阻断。间接免疫荧光分析显示，SLE T细胞内的肿瘤坏死因子-α水平显著低于对照组。这些数据表明，SLE患者活化的T细胞对TCR介导的死亡刺激具有相对抵抗力，尽管它们表现出完整的抗Fas单抗介导的细胞死亡。缺陷抗原介导的细胞死亡可能导致狼疮患者激活的自身反应细胞数量增加。(C)1996年学术出版社。
Activation-induced cell death (AICD) plays an important role in the regulation of the immune response by eliminating preactivated and potentially autoreactive cells. To elucidate possible abnormalities of AICD in human systemic lupus erythematosus (SLE), we studied AICD in activated T cells from patients with SLE and normal controls. CD3-mediated cell death was determined in short-term T cell lines by flow cytometry using propidium iodide staining and analysis of DNA subdiploid peak populations. It was found to be significantly lower in T cells from SLE patients compared to cells from normal controls. Anti-Fas mAb-mediated cell death was similar in SLE and control cell lines. CD3-mediated AICD could be blocked in control and SLE T cell lines by an IgG anti-Fas mAb. Indirect immunofluorescence analysis showed statistically significantly less intracellular TNF-alpha in SLE T cells than in control cells. These data show that activated T cells from patients with SLE are relatively resistant to a TCR-mediated death stimulus although they display intact anti-Fas mAb-mediated cell death. Defective antigen-mediated cell death can contribute to increased numbers of activated autoreactive cells in lupus patients. (C) 1996 Academic Press, Inc.