Grell M, Scheurich P, Meager A, Pfizenmaier K
Institute for Cell Biology and Immunology, University of Stuttgart, Germany.
Lymphokine Cytokine Res. 1993 Jun;12(3):143-8.
The human rhabdomyosarcoma cell line KYM-1 coexpresses high numbers of both tumor necrosis factor-alpha (TNF) receptors, TR60 and TR80, and is highly sensitive to TNF-induced cytotoxicity. We show here that each receptor type can mediate cytotoxicity on its own on selective stimulation. This was achieved using receptor specific antibodies, able to compete with ligand binding to the respective receptor molecules. Thus, the TR60-specific monoclonal antibody H398 was strongly agonistic, i.e., cytotoxic, in the presence of a secondary cross-linking immunoglobulin. Selective stimulation of TR80 by antibody-mediated receptor crosslinking also induced strong cytotoxicity in KYM-1 cells. Interestingly, when both receptor subsets were stimulated in parallel by limited receptor cross-linking, additive cytolytic effects were observed. In each case the respective Fab fragments showed no agonistic activity. When the natural ligand TNF was used to induce cytolysis, blocking studies with receptor specific Fab fragments indicated that the main cytotoxic effect of TNF is mediated via TR60, although these receptors represent only about 8% of the total TNF receptor number.
人横纹肌肉瘤细胞系KYM-1共表达大量肿瘤坏死因子-α（TNF）受体TR60和TR80，并且对TNF诱导的细胞毒性高度敏感。我们在此表明，每种受体类型在选择性刺激下自身均可介导细胞毒性。这是通过使用能够与配体结合各自受体分子竞争的受体特异性抗体实现的。因此，TR60特异性单克隆抗体H398在存在二级交联免疫球蛋白的情况下具有强烈的激动作用，即细胞毒性。通过抗体介导的受体交联对TR80进行选择性刺激也可在KYM-1细胞中诱导强烈的细胞毒性。有趣的是，当通过有限的受体交联同时刺激两个受体亚群时，观察到相加的溶细胞作用。在每种情况下，各自的Fab片段均无激动活性。当使用天然配体TNF诱导细胞溶解时，用受体特异性Fab片段进行的阻断研究表明，TNF的主要细胞毒性作用是通过TR60介导的，尽管这些受体仅占总TNF受体数量的约8%。
