IL-12 plays a significant role in the apoptosis of human T cells in the absence of antigenic stimulation.
IL-12 plays a significant role in the apoptosis of human T cells in the absence of antigenic stimulation.
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DOI：
10.1006/cyto.2002.1958
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发表时间：
2002-08
期刊：
影响因子：
3.8
通讯作者：
H. Fan;C. Walters;G. Dunston;R. Tackey
中科院分区：
文献类型：
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作者：
H. Fan;C. Walters;G. Dunston;R. Tackey
白细胞介素-12（IL-12）是一种免疫调节细胞因子，在细胞介导的免疫中起重要作用。已知其在体内系统如移植物抗宿主病（GVHD）和实验性自身免疫性葡萄膜炎（EAU）中诱导T细胞凋亡。然而，在缺乏抗原刺激的情况下IL-12在T细胞凋亡中的作用尚未明确定义。本研究旨在研究在不存在抗原的情况下，IL-12是否能够诱导T细胞凋亡，以及IL-12所利用的哪些信号通路参与了这一过程。我们的数据清楚地表明，IL-12在不存在抗原的情况下诱导T细胞凋亡。流式细胞术和ELISA显示IL-12处理的T细胞中FasL上调和IFN-γ合成增加，而Fas和TNF-R1几乎没有变化。半定量RT-PCR显示IL-12能够上调TNF-α和FasL mRNA的表达。IL-12诱导的细胞凋亡与caspase-3、caspase-2、caspase-7、DNA片段化因子45（DFF 45）和Fas相关死亡结构域（FADD）有关，而与TNF受体相关死亡结构域（TRADD）和受体相互作用蛋白（RIP）无关。抑制Janus酪氨酸激酶（JAK）能够抑制IL-12诱导的T细胞凋亡。抗FasL抗体能阻断IL-12诱导的T细胞凋亡。总之，我们的研究结果表明，IL-12能够诱导T细胞凋亡的抗原的情况下。此外，目前的数据表明，这一过程是FasL介导的和caspase-3依赖。此外，JAK被证明参与了这一过程。这些结果可能对理解IL-12介导的T细胞凋亡具有重要意义。
Interleukin-12 (IL-12) is an immunoregulatory cytokine that plays an essential role in cell-mediated immunity. It is known to induce T cell apoptosis in in vivo systems such as graft-versus-host disease (GVHD) and experimental autoimmune uveitis (EAU). However, the role of IL-12 in T cell apoptosis in the absence of antigenic stimulation has not been clearly defined. This study was conducted to investigate whether IL-12, in the absence of an antigen, is able to induce T cell apoptosis, and also, which signalling pathways utilized by IL-12 are involved in this process. Our data clearly showed that IL-12 in the absence of an antigen induces apoptosis in T cells. Flow cytometry and ELISA showed FasL up-regulation and increased IFN-gamma synthesis in IL-12 treated T cells, while Fas and TNF-R1 showed little change. Semi-quantitative RT-PCR demonstrated that IL-12 was able to up-regulate TNF-alpha and FasL mRNA expression. Furthermore, IL-12 induced apoptosis was associated with caspase-3, caspase-2, caspase-7, DNA fragmentation factor 45 (DFF45) and Fas associated death domain (FADD) whereas TNF receptor associated death domain (TRADD) and receptor interacting protein (RIP) were not. Inhibition of Janus tyrosine kinase (JAK) was able to suppress IL-12 induced T cell apoptosis. Anti-FasL antibody was able to block IL-12 induced T cell apoptosis. In conclusion, our findings suggest that IL-12 is able to induce T cell apoptosis in the absence of an antigen. In addition, the present data suggest that this process is FasL mediated and caspase-3 dependent. Furthermore, JAK was shown to be involved in this process. These results may have significant implications in the understanding of IL-12 mediated T cell apoptosis.