Limited importance of CD40/CD40L interaction in the B7-dependent generation of anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells stimulated in vitro in the presence of tumor necrosis factor.
Limited importance of CD40/CD40L interaction in the B7-dependent generation of anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells stimulated in vitro in the presence of tumor necrosis factor.
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CD40/CD40L 相互作用在肿瘤坏死因子存在下体外刺激的肿瘤携带者脾细胞产生 B7 依赖性抗 MOPC-315 细胞毒性 T 淋巴细胞活性中的重要性有限。
DOI：
10.1007/s002620050490
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发表时间：
1998
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：
Kalinichenko,TV;Mokyr,MB
我们之前已经阐明了B7-2表达对于通过添加肿瘤坏死因子α (TNFα)的荷瘤脾细胞的刺激培养增强细胞毒性T淋巴细胞（CTL）活性的重要性。在这里，我们表明B7-1分子对这种刺激培养的CTL生成也很重要，尽管其程度远低于B7-2分子。此外，我们证明了CD40/CD40L相互作用对B7-2分子表达的重要性，而不是B7-1分子，在TNF存在的体外刺激下，由肿瘤载体脾细胞表达。CD40/CD40L的相互作用也被证明是重要的产生CTL活性的肿瘤携带脾细胞在外源性TNF存在的体外刺激。然而，CD40/CD40L相互作用对于CTL活性增强的产生的重要性不如B7-2水平升高的表达。具体而言，阻断CD40/CD40L相互作用，使体外刺激肿瘤载体脾细胞在TNF存在下表达的B7-2水平降低到体外刺激肿瘤载体脾细胞在无外源TNF的情况下表达的B7-2水平，但未能使CTL产生的水平降低到体外刺激肿瘤载体脾细胞在无外源TNF的情况下产生的水平。最后，阻断CD40/CD40L相互作用在抑制外源性TNF刺激下肿瘤载体脾细胞产生CTL活性方面不如阻断B7-2/CD28相互作用。因此，尽管CD40/CD40L相互作用对于通过添加了TNF的肿瘤载体脾细胞的刺激培养产生增强的CTL活性是重要的，TNF也通过其他独立于CD40/CD40L相互作用但依赖于B7-2表达的机制介导其通过这种刺激培养产生CTL的增强作用。
We have previously illustrated the importance of B7-2 expression for the enhanced generation of cytotoxic T lymphocyte (CTL) activity by stimulation cultures of tumor bearer splenic cells to which tumor necrosis factor α (TNFα) has been added. Here we show that the B7-1 molecule is also important for CTL generation by such stimulation cultures, although to a much lesser extent than the B7-2 molecule. In addition, we show the importance of CD40/CD40L interaction for the expression of the B7-2 molecule, but not the B7-1 molecule, by tumor bearer splenic cells stimulated in vitro in the presence of TNF. The CD40/CD40L interaction is also shown to be important for the generation of CTL activity by tumor bearer splenic cells stimulated in vitro in the presence of exogenous TNF. However, the CD40/CD40L interaction is less important for the generation of enhanced CTL activity than for the expression of an elevated level of B7-2. Specifically, blockade of CD40/CD40L interaction, which reduced the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the presence of TNF to the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the absence of exogenous TNF, failed to reduce the level of CTL generated to the level generated by tumor bearer splenic cells stimulated in the absence of exogenous TNF. Finally, blockade of CD40/CD40L interaction was inferior to blockade of B7-2/CD28 interaction in inhibiting the generation of CTL activity by tumor bearer splenic cells stimulated in the presence of exogenous TNF. Thus, although CD40/CD40L interaction is important for the generation of enhanced CTL activity by stimulation cultures of tumor bearer splenic cells to which TNF has been added, TNF also mediates its potentiating effect for CTL generation by such stimulation cultures via other mechanisms that are independent of CD40/CD40L interaction but dependent on B7-2 expression.