CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.
CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.
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DOI：
10.1182/blood.v88.4.1375.bloodjournal8841375
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发表时间：
1996-08
期刊：
影响因子：
20.3
通讯作者：
E. Schattner;J. Mascarenhas;J. Bishop;D. Yoo;A. Chadburn;M. Crow;S. Friedman
中科院分区：
文献类型：
--
作者：
E. Schattner;J. Mascarenhas;J. Bishop;D. Yoo;A. Chadburn;M. Crow;S. Friedman
CD 4 + Th 1细胞的细胞毒作用由Fas（CD 95，APO-1）及其配体（Fas ligand）介导。最近使用未转化的B细胞和拉莫斯Burkitt淋巴瘤（BL）B细胞系细胞的研究表明，通过活化的、携带CD 40配体（CD 40 L）的CD 4 + T细胞在B细胞表面的CD 40连接上调了B细胞上的Fas表达，并引发了B细胞的Fas介导的死亡信号。在这项工作中，我们研究了这种Fas上调和B细胞凋亡的CD 4 + T细胞依赖性分子途径是否反映了拉莫斯B细胞系的特殊性，或者也适用于其他伯基特肿瘤。在检查的6个EB病毒阴性BL细胞系中的5个中，细胞组成性地表达不可检测的或低水平的Fas，并且对由单克隆抗Fas抗体诱导的Fas介导的信号具有抗性。所有6种BL细胞系B细胞上调Fas以响应CD 40连接，并且在4种情况下，它们变得对Fas介导的死亡信号敏感。在一个BL细胞系中，细胞对Fas介导的细胞溶解组成型敏感，并且不受CD 40信号的影响。接下来，我们将这些免疫操作应用于来自难治性临床样品的细胞，并观察到在我们的系统中肿瘤细胞可以被诱导表达Fas并进行凋亡。这些结果确立了CD 4 + T细胞和Fas-Fas配体系统作为伯基特淋巴瘤B细胞的重要免疫调节因子，并表明肿瘤细胞对Fas介导的死亡信号的易感性可通过细胞表面的特异性活化事件来调节。
Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)-bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B-cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas-mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.