CD47 signals T cell death.
CD47 signals T cell death.
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DOI：
10.4049/jimmunol.162.12.7031
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发表时间：
1999-06
影响因子：
4.4
通讯作者：
Rolf D. Pettersen;K. Hestdal;M. K. Olafsen;Sverre O. Lie;Frederik P. Lindberg
中科院分区：
文献类型：
--
作者：
Rolf D. Pettersen;K. Hestdal;M. K. Olafsen;Sverre O. Lie;Frederik P. Lindberg
活化诱导的T细胞死亡调节免疫应答，并被认为涉及Fas和TNF受体连接诱导的细胞凋亡。其他受体在T细胞死亡信号中的作用尚不清楚。在这项研究中，我们证明，激活CD 47的IG可变结构域上的特异性表位迅速诱导T细胞凋亡。一种新的单克隆抗体，Ad 22，该网站诱导Jurkat细胞和CD 3 ε刺激的PBMC的凋亡，如确定的形态学变化，磷脂酰丝氨酸暴露在细胞表面，碘化丙啶的摄取，并通过流式细胞术的真实计数。与此相反，在分别针对远距离或近距离相邻区域的抗CD 47 mAb 2D 3或B6 H12培养后未观察到细胞凋亡。CD 47介导的细胞死亡不依赖于CD 3、CD 4、CD 45或p56 lck参与，如对这些信号传导途径缺陷的变体Jurkat细胞系的研究所证明的。然而，CD 3 β和CD 47的共连接增强了具有功能性CD 3 β的Jurkat细胞上的磷脂酰丝氨酸外化。此外，正常的T细胞需要预活化以响应CD 47诱导的凋亡。CD 47介导的细胞死亡似乎独立于Fas或TNF受体信号传导，并且不涉及特征性DNA片段化或对IL-1 β转化酶样蛋白酶或CPP 32的需求。综上所述，我们的数据表明，在适当的条件下，CD 47活化导致非常快速的T细胞死亡，显然是由一种新的凋亡途径介导的。因此，CD 47可能关键地参与控制活化的T细胞的命运。
Activation-induced death of T cells regulates immune responses and is considered to involve apoptosis induced by ligation of Fas and TNF receptors. The role of other receptors in signaling T cell death is less clear. In this study we demonstrate that activation of specific epitopes on the Ig variable domain of CD47 rapidly induces apoptosis of T cells. A new mAb, Ad22, to this site induces apoptosis of Jurkat cells and CD3epsilon-stimulated PBMC, as determined by morphological changes, phosphatidylserine exposure on the cell surface, uptake of propidium iodide, and true counts by flow cytometry. In contrast, apoptosis was not observed following culture with anti-CD47 mAbs 2D3 or B6H12 directed to a distant or closely adjacent region, respectively. CD47-mediated cell death was independent of CD3, CD4, CD45, or p56lck involvement as demonstrated by studies with variant Jurkat cell lines deficient in these signaling pathways. However, coligation of CD3epsilon and CD47 enhanced phosphatidylserine externalization on Jurkat cells with functional CD3. Furthermore, normal T cells required preactivation to respond with CD47-induced apoptosis. CD47-mediated cell death appeared to proceed independent of Fas or TNF receptor signaling and did not involve characteristic DNA fragmentation or requirement for IL-1beta-converting enzyme-like proteases or CPP32. Taken together, our data demonstrate that under appropriate conditions, CD47 activation results in very rapid T cell death, apparently mediated by a novel apoptotic pathway. Thus, CD47 may be critically involved in controlling the fate of activated T cells.