Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells
Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells
复制标题
DOI：
10.1182/blood-2003-10-3684
复制
发表时间：
2005-04-15
期刊：
影响因子：
20.3
通讯作者：
Kipps, TJ
中科院分区：
文献类型：
--
作者：
Dicker, F;Kater, AP;Kipps, TJ
慢性淋巴细胞白血病（CLL）B细胞在CD 40连接后3 ~ 5天对Fas（CD 95）介导的凋亡变得敏感。然而，CD 4（+）细胞毒性T淋巴细胞（CTL）可在CD 40交联后24小时内通过Fas配体（CD 178）依赖性过程杀死CLL B细胞，此时单独连接CD 95不足以诱导凋亡。除CD 95外，CD 40激活的CLL细胞还表达DRS，DRS是由CD 4（+）CTL表达的肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）的受体。此外，体外和体内CD 40连接诱导CLL细胞表达促凋亡蛋白，BH 3相互作用结构域死亡激动剂（Bid），其可以促进细胞依赖性凋亡诱导途径和死亡受体（如死亡受体5（DR 5））之间的串扰。为了评估CD 95和/或DR 5的连接是否可以诱导CD 40活化的CLL细胞的凋亡，我们产生了表达人TRAIL和CD 178（中国仓鼠卵巢[CHO]-CD 178/TRAIL）或仅表达TRAIL（CHO-TRAIL）或CD 178（CHO-CD 178）的人工细胞毒性效应细胞。CHO-CD 178/TRAIL细胞在杀伤CD 40激活的CLL细胞方面比CHO-TRAIL或CHO-CD 178显著更有效，并且与后者不同，CHO-CD 178/TRAIL细胞可以在CD 40连接后24小时杀伤CLL细胞。我们的结论是，CD 40连接诱导CLL细胞表达促凋亡分子Bid和死亡受体CD 95和DR 5，后者可以协同作用，诱导caspase依赖性凋亡的CD 40激活的CLL B细胞。(c)2005年，美国血液学会。
Chronic lymphocytic leukemia (CLL) B cells become sensitive to Fas (CD95)-mediated apoptosis 3 to 5 days after CD40 ligation. However, CD4(+) cytotoxic T lymphocytes (CTLs) can kill CLL B cells via a Fas-ligand (CD178)-dependent process within 24 hours after CD40 cross-linking, when ligation of CD95 alone is insufficient to induce apoptosis. In addition to CD95, CD40-activated CLL cells also express DRS, a receptor for tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) that is expressed by CD4(+) CTL. In addition, CD40 ligation in vitro and in vivo induces CLL cells to express the proapoptotic protein, BH3 interacting domain death agonist (Bid), which can facilitate crosstalk between mitochondrial-dependent, apoptosis-inducing pathways and death receptors, such as death receptor 5 (DR5). To evaluate whether ligation of CD95 and/or DR5 can induce apoptosis of CD40-activated CLL cells, we generated artificial cytotoxic effector cells that express both human TRAIL and CD178 (Chinese hamster ovary [CHO]-CD178/TRAIL) or only TRAIL (CHO-TRAIL) or CD178 (CHO-CD178). CHO-CD178/TRAIL cells were significantly more effective in killing CD40-activated CLL cells than either CHO-TRAIL or CHO-CD178 and, unlike the latter, could kill CLL cells 24 hours after CD40 ligation. We conclude that CD40 ligation induces CLL cells to express the proapoptotic molecule Bid and the death receptors CD95 and DR5, the latter of which can act synergistically to induce caspase-dependent apoptosis of CD40-activated CLL B cells. (c) 2005 by The American Society of Hematology.