CD99 signals caspase-independent T cell death
CD99 signals caspase-independent T cell death
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DOI：
10.4049/jimmunol.166.8.4931
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发表时间：
2001-04-15
影响因子：
4.4
通讯作者：
Lie, SO
中科院分区：
文献类型：
--
作者：
Pettersen, RD;Bernard, G;Lie, SO
通过Fas和TNF受体的死亡信号传导在活化的成熟T细胞的控制中起主要作用。然而，死亡受体的性质，它可以被免疫系统用来控制T细胞还没有获得对Fas配体或TNF的敏感性，是没有建立。在这项研究中，我们证明了CD99上不同表位的参与通过一种新的非半胱天冬酶依赖性途径快速诱导T细胞死亡。这些CD99表位的新mAb Ad20诱导转化T细胞的程序性细胞死亡，如通过形态学变化、细胞表面的磷脂酰丝氨酸暴露和碘化丙啶摄取所确定的。一般来说，与抗Fas和TNF相关凋亡诱导配体（TRAIL）的影响相比，CD99的连接诱导了动力学上更快和更深刻的死亡反应。观察到Ad20诱导的程序性细胞死亡与7的8个T细胞系检查，值得注意的是，只有其中两个是明显响应于抗Fas和TRAIL。CD99介导的死亡信号传导独立于功能性CD3、CD4、CD45和p56（lck）进行，揭示了与CD47介导的T细胞死亡应答的区别，并且不受CD47信号传导干扰的影响。与对转化T细胞系的作用相反，在正常外周T细胞中未观察到Ad20诱导的死亡反应。因此，我们的数据表明，CD99与一种新的死亡途径有关，该途径可能在控制早期T细胞方面具有生物学相关性。
Death signaling by Fas and TNF receptors plays a major role in the control of activated mature T cells. However, the nature of the death receptors, which may be used by the immune system to control T cells that have not acquired susceptibility to Fas ligand or TNF, is not established. In this study, we demonstrate that engagement of distinct epitopes on CD99 rapidly induces T cell death by a novel caspase-independent pathway. A new mAb to these CD99 epitopes, Ad20, induces programmed cell death of transformed T cells as determined by morphological changes, phosphatidylserine exposure on the cell surface, and uptake of propidium iodide. In general, ligation of CD99 induced kinetically faster and more profound death responses as compared with the impact of anti-Fas and TNF-related apoptosis-inducing ligand (TRAIL). Ad20-induced programmed cell death was observed with seven of eight T cell lines examined, and notably, only two of these were distinctly responsive to anti-Fas and TRAIL. CD99-mediated death signaling proceeded independently of functional CD3, CD4, CD45, and p56(lck), revealed distinctions from CD47-mediated T cell death responses, and was not influenced by interference with CD47 signaling. In contrast to the effect on transformed T cell lines, Ad20-induced death responses were not observed with normal peripheral T cells. Thus, our data suggest that CD99 is linked to a novel death pathway that may have biologic relevance in control of early T cells.