Activation-induced cell death in murine T cell hybridomas. Differential regulation of Fas (CD95) versus Fas ligand expression by cyclosporin A and FK506.
Activation-induced cell death in murine T cell hybridomas. Differential regulation of Fas (CD95) versus Fas ligand expression by cyclosporin A and FK506.
复制标题
小鼠 T 细胞杂交瘤中激活诱导的细胞死亡。
DOI：
10.1093/intimm/8.7.1017
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发表时间：
1996
影响因子：
4.4
通讯作者：
Green,DR
中科院分区：
文献类型：
--
作者：
Brunner,T;Yoo,NJ;LaFace,D;Ware,CF;Green,DR
我们以前曾报道，小鼠T细胞杂交瘤的激活会导致Fas(CD95)及其配体(FasL)的表达，这些表达随后会相互作用，即使是在同一细胞上，也会导致细胞凋亡。由于免疫抑制药物环孢素A(CsA)和FK506阻断了活化诱导的T细胞杂交瘤细胞的凋亡，我们研究了这些化合物是否通过干扰Fas、FasL或两者的表达来影响细胞死亡，或者它们是否阻断了Fas信号转导。我们发现CsA和FK5O6处理的细胞在激活后没有表现出FasL mRNA的转录，并且通过染色和诱导Fas+靶细胞凋亡的能力来确定其表面缺乏功能性的FasL蛋白。相反，在CsA或FK506存在下激活的细胞中，没有观察到对Fas mRNA表达的抑制。然而，令人惊讶的是，在免疫抑制药物存在下激活的细胞表面Fas水平始终低于激活细胞，这表明Fas表达在几个水平上受到调节。然而，在CsA或FK5O6存在下激活的细胞在抗Fas抗体处理后发生了凋亡，而未激活的细胞则没有。此外，CsA和FK506不干扰Fas信号转导，因为抗Fas诱导的Fas+靶细胞的凋亡不受这些药物的影响。因此，我们得出结论，CsA和FK506主要通过干扰导致FasL表达的激活信号来阻断激活诱导的T细胞杂交瘤的凋亡，并且进一步地，对激活的T细胞上Fas和FasL的表达的调控是不同的。
We have previously reported that activation of murine T cell hybridomas leads to expression of Fas (CD95) and its ligand (FasL) which subsequently interact, even on the same cell, leading to apoptotic cell death. Since the immunosuppressive drugs cyclosporin A (CsA) and FK506 block activation-induced apoptosis in T cell hybridomas, we examined whether such compounds affect cell death by interfering with expression of Fas, FasL or both, or whether they block Fas signal transduction. We have found that CsA- and FK5O6-treated cells did not exhibit transcription of FasL mRNA after activation and were lacking functional FasL protein on their surface as determined by staining and the ability to induce apoptosis in Fas+target cells. In contrast, no inhibition of the elevated Fas mRNA expression was observed in cells activated in the presence of CsA or FK506. Surprisingly, however, cell surface Fas levels were consistently lower on cells activated in the presence of immunosuppressive drugs than on activated cells, suggesting that Fas expression is regulated at several levels. Nevertheless, cells activated in the presence of CsA or FK5O6 underwent apoptosis upon treatment with anti-Fas antibody, while unactivated cells did not. Furthermore, CsA and FK506 do not interfere with Fas signaling since anti-Fas induced apoptosis in Fas+target cells was unaffected by these drugs. We therefore conclude that CsA and FK506 block activation-induced apoptosis in T cell hybridomas predominantly by interfering with activation signals leading to FasL expression and, further, that the regulation of the expression of Fas and FasL on activated T cells is differentially controlled.