Kalinichenko T V, Mokyr M B
Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 60612, USA.
Cancer Immunol Immunother. 1998 Aug;46(6):293-303. doi: 10.1007/s002620050490.
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 alpha (TNFalpha) 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.
我们之前已经阐述了B7-2表达对于增强细胞毒性T淋巴细胞（CTL）活性的重要性，该活性通过对添加了肿瘤坏死因子α（TNFα）的荷瘤小鼠脾细胞进行刺激培养而产生。在此我们表明，B7-1分子对于此类刺激培养产生CTL也很重要，尽管其程度远低于B7-2分子。此外，我们显示了CD40/CD40L相互作用对于在TNF存在下体外刺激的荷瘤小鼠脾细胞表达B7-2分子的重要性，但对于B7-1分子表达并不重要。CD40/CD40L相互作用还被证明对于在存在外源性TNF的情况下体外刺激的荷瘤小鼠脾细胞产生CTL活性很重要。然而，CD40/CD40L相互作用对于增强CTL活性的产生不如对B7-2高水平表达那么重要。具体而言，阻断CD40/CD40L相互作用，可使在TNF存在下体外刺激的荷瘤小鼠脾细胞表达的B7-2水平降低至在无外源性TNF情况下体外刺激的荷瘤小鼠脾细胞表达的B7-2水平，但未能将产生的CTL水平降低至在无外源性TNF情况下刺激的荷瘤小鼠脾细胞所产生的水平。最后，在抑制存在外源性TNF时刺激的荷瘤小鼠脾细胞产生CTL活性方面，阻断CD40/CD40L相互作用不如阻断B7-2/CD28相互作用有效。因此，尽管CD40/CD40L相互作用对于对添加了TNF的荷瘤小鼠脾细胞进行刺激培养以增强CTL活性很重要，但TNF也通过其他独立于CD40/CD40L相互作用但依赖于B7-2表达的机制介导其对此类刺激培养产生CTL的增强作用。
