Signaling through CD40 enhances cytotoxic T lymphocyte generation by CD8+ T cells from mice bearing large tumors.
Signaling through CD40 enhances cytotoxic T lymphocyte generation by CD8+ T cells from mice bearing large tumors.
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通过 CD40 发出的信号增强了来自患有大肿瘤的小鼠的 CD8 T 细胞产生的细胞毒性 T 淋巴细胞。
DOI：
10.1007/s002620050560
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Mokyr,MB
中科院分区：
文献类型：
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作者：
Donepudi,M;Quach,DD;Mokyr,MB
最近的研究表明，CD40/CD154(CD40L)相互作用在产生细胞介导的抗肿瘤免疫反应中具有重要意义。在这里，我们表明通过CD40的信号(通过使用激活的抗CD40单抗，1C10)实际上可以促进CD8+脾T细胞在体外产生CTL活性，这些T细胞来自于荷有大的MOPC-315肿瘤的小鼠。为了充分发挥其对细胞毒性T淋巴细胞(CTL)产生的增强作用，必须在荷瘤脾细胞的刺激培养开始时加入抗CD40单抗，提示CD40信号在抗肿瘤细胞毒的诱导阶段具有重要作用。此外，抗CD40单抗可增强B220+细胞(即B细胞)表面B7-2(CD86)和B7-1(CD80)共刺激分子的表达，而B7-2和B7-1分子在增强抗CD40单抗对荷瘤小鼠脾细胞产生CTL的作用中起重要作用。此外，B220+细胞对抗CD40单抗的增强作用是必不可少的，因为诱导阶段B220+细胞的耗尽完全丧失了抗CD40单抗促进CTL生成的能力。因此，通过CD40的信号通过上调B7-2和B7-1在B220+细胞上的表达来促进CD8+T细胞从荷瘤小鼠产生CTL。
Recent studies have demonstrated the importance of CD40/CD154 (CD40L) interactions for the generation of cell-mediated antitumor immune responses. Here we show that signaling via CD40 (through the use of the activating anti-CD40 mAb, 1C10) can actually promote the in vitro generation of CTL activity by CD8+splenic T cells from mice bearing a large MOPC-315 tumor. Anti-CD40 mAb had to be added at the initiation of the stimulation cultures of tumor-bearing splenic cells in order to realize fully its potentiating activity for cytotoxic T lymphocyte (CTL) generation, suggesting that signaling through CD40 is important at the inductive stage of antitumor cytotoxicity. Moreover, anti-CD40 mAb was found to enhance the expression of the B7-2 (CD86) and, to a lesser extent, the B7-1 (CD80) costimulatory molecules on B220+cells (i.e., B cells), and B7-2 and, to a lesser extent, B7-1 molecules played an important role in the potentiating effect of anti-CD40 mAb for CTL generation by tumor-bearer splenic cells. Furthermore, B220+cells were found to be essential for the potentiating effect of anti-CD40 mAb, as depletion of B220+cells at the inductive stage completely abrogated the ability of anti-CD40 mAb to enhance CTL generation. Thus, signaling through CD40 enhances CTL generation by CD8+T cells from tumor-bearing mice by a mechanism that involves the up-regulation of B7-2 and, to a lesser extent, B7-1 expression on B220+cells.