Wright S C, Bonavida B
J Immunol. 1983 Jun;130(6):2965-8.
The effects of interferon (IFN) at the level of the target cell in the natural killer cytotoxic factors (NKCF) system have been examined to determine whether they correlate with the effects of IFN in natural killer (NK) cell-mediated cytotoxicity (CMC). NKCF are released into the supernatant of co-cultures of murine spleen cells and YAC-1 stimulator cells, and their lytic activity is measured against YAC-1 target cells. It was found that IFN-pretreated YAC-1 target cells were still sensitive to lysis by NKCF, although their ability to stimulate release of NKCF from murine spleen cells was impaired. This defect was not due to a lack of NK target structures, because IFN-pretreated YAC-1 cells form a normal number of conjugates with spleen cells. The defect also could not be attributed to an IFN-induced inhibition of protein synthesis, because emetine-pretreated YAC-1 stimulator cells can still induce the release of high levels of NKCF. Cellfree supernatants containing NKCF also contain low levels of endogenous IFN (10 to 50 U/ml). Although this concentration of IFN itself is not toxic to YAC-1 cells, it may still interact with NKCF and/or the target cell to enhance cytotoxicity mediated by NKCF. Evidence in support of this possibility is derived from experiments that demonstrated that addition of exogenous IFN to NKCF resulted in a synergistic enhancement of cytotoxicity. Taken together, these findings can account for the IFN-induced inhibition of target cell susceptibility to lysis in the NK CMC system. In addition, the evidence supports our model for the role of NKCF in the mechanism of NK CMC. According to this model, the effector cell must first bind to the target cell; then the target cell delivers a signal to the effector cell to activate the NKCF release mechanism. The effector cell releases NKCF that then bind to the target cell and mediate cell lysis. The mechanism by which IFN-pretreated target cells become relatively NK-resistant appears to be a defect in their ability to stimulate the effector cell to release NKCF after the initial effector-target cell binding.
研究了干扰素（IFN）在自然杀伤细胞毒性因子（NKCF）系统中对靶细胞水平的影响，以确定它们是否与IFN在自然杀伤（NK）细胞介导的细胞毒性（CMC）中的作用相关。NKCF被释放到小鼠脾细胞与YAC-1刺激细胞共培养的上清液中，并测定其对YAC-1靶细胞的裂解活性。结果发现，经IFN预处理的YAC-1靶细胞对NKCF的裂解仍敏感，尽管其刺激小鼠脾细胞释放NKCF的能力受损。这种缺陷并非由于缺乏NK靶结构，因为经IFN预处理的YAC-1细胞与脾细胞形成的结合物数量正常。该缺陷也不能归因于IFN诱导的蛋白质合成抑制，因为经依米丁预处理的YAC-1刺激细胞仍能诱导高水平NKCF的释放。含有NKCF的无细胞上清液中也含有低水平的内源性IFN（10至50 U/ml）。尽管这种浓度的IFN本身对YAC-1细胞无毒，但它仍可能与NKCF和/或靶细胞相互作用，以增强由NKCF介导的细胞毒性。支持这种可能性的证据来自实验，这些实验表明向NKCF中添加外源性IFN会导致细胞毒性的协同增强。综上所述，这些发现可以解释IFN诱导的NK CMC系统中靶细胞对裂解敏感性的抑制。此外，证据支持我们关于NKCF在NK CMC机制中作用的模型。根据该模型，效应细胞必须首先与靶细胞结合；然后靶细胞向效应细胞传递信号以激活NKCF释放机制。效应细胞释放NKCF，然后NKCF与靶细胞结合并介导细胞裂解。经IFN预处理的靶细胞相对抗NK的机制似乎是在最初的效应细胞-靶细胞结合后，它们刺激效应细胞释放NKCF的能力存在缺陷。
