Interferon gamma plays a critical role in induced cell death of effector T cell: a possible third mechanism of self-tolerance.
Interferon gamma plays a critical role in induced cell death of effector T cell: a possible third mechanism of self-tolerance.
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DOI：
10.1084/jem.172.6.1735
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发表时间：
1990-12-01
期刊：
影响因子：
--
通讯作者：
Janeway CA Jr
中科院分区：
文献类型：
--
作者：
Liu Y;Janeway CA Jr
我们使用抗 T 细胞单克隆抗体 (mAb) 作为模拟配体，研究在存在或不存在辅助细胞的情况下克隆 1 型辅助 T 细胞的 T 细胞受体 (TCR) 连接的影响。我们的结果表明，在没有辅助细胞的情况下 TCR 的连接会迅速诱导细胞死亡。通过添加脾贴壁细胞可以防止细胞死亡，从而导致强烈的克隆扩增。诱导的细胞死亡被环孢菌素A和抗干扰素γ(IFN-γ)抑制，并且通过向环孢菌素A处理的细胞中添加外源重组IFN-γ来恢复。这些结果表明，在缺乏共刺激细胞的情况下，IFN-γ 在抗 TCR mAb 诱导的细胞死亡中发挥着关键作用。我们提出，除了发育中自身反应性T细胞的胸腺内缺失和成熟、初始T细胞的外周失活之外，活性效应T细胞的诱导细胞死亡提供了第三种耐受机制。
We have used anti-T cell monoclonal antibodies (mAbs) as mimic ligands to study the effects of T cell receptor (TCR) ligation of cloned T helper type 1 cells in the presence or absence of accessory cells. Our results demonstrate that ligation of the TCR in the absence of accessory cells rapidly induces cell death. Cell death can be prevented by addition of spleen adherent cells, leading to strong clonal expansion. Induced cell death is inhibited by cyclosporin A and by anti- interferon gamma (IFN-gamma), and is restored by adding exogenous recombinant IFN-gamma to cyclosporin A-treated cells. These results demonstrate that IFN-gamma plays a critical role in cell death induced by anti-TCR mAbs in the absence of costimulatory cells. We propose that induced cell death of active effector T cells provides a third mechanism of tolerance in addition to intrathymic deletion of developing autoreactive T cells and peripheral inactivation of mature, naive T cells.