Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Exp Mol Med. 2010 May 31;42(5):353-65. doi: 10.3858/emm.2010.42.5.037.
Here, we show that the interaction between two membrane proteins, the mouse homologue of CD99 (designated D4) and its ligand, paired immunoglobulin-like type 2 receptor (PILR), is one of the major mechanisms of thymocyte apoptosis. Using the polymeric fusion protein of PILR and IgG1 (PILR-Ig), we demonstrated that D4 ligation in the absence of T cell receptor (TCR) engagement leads to the induction of apoptosis, mainly at the double-positive stage of thymocytes. This was further confirmed by a blocking study in which blocking the interaction between D4 and PILR by soluble D4 protein led to reduced apoptosis in the fetal thymic organ culture with wild type and TCRalpha(-/-) mice. Furthermore, the dissection of intracellular signaling pathway demonstrated that D4 cross-linking led to caspase activation without any change in mitochondrial membrane potential. Based on these data, we propose a mechanism for thymocyte depletion in which the interaction between D4 and PILR delivers an active signal.
在这里，我们表明，两种膜蛋白——小鼠同源物 CD99（命名为 D4）及其配体配对免疫球蛋白样型 2 受体（PILR）之间的相互作用是胸腺细胞凋亡的主要机制之一。我们利用 PILR 和 IgG1 的聚合融合蛋白（PILR-Ig）证明，在没有 T 细胞受体（TCR）结合的情况下，D4 的连接导致凋亡的诱导，主要发生在胸腺细胞的双阳性阶段。这进一步通过阻断研究得到证实，其中通过可溶性 D4 蛋白阻断 D4 和 PILR 之间的相互作用导致野生型和 TCRalpha(-/-)小鼠的胎胸腺器官培养中的凋亡减少。此外，细胞内信号通路的剖析表明，D4 交联导致 caspase 激活，而线粒体膜电位没有任何变化。基于这些数据，我们提出了一种胸腺细胞耗竭的机制，其中 D4 和 PILR 之间的相互作用传递了一个活性信号。
