Wong G H, Tartaglia L A, Lee M S, Goeddel D V
Department of Immunology, Genentech, Inc., South San Francisco, CA 94080.
J Immunol. 1992 Nov 15;149(10):3350-3.
Agonist antibodies (Ab) to the two TNF receptors, TNF-R1 (55 kDa) and TNF-R2 (75 kDa), have been shown to signal many of the distinct functions induced by TNF-alpha. We have found that anti-TNF-R1, but not anti-TNF-R2, Ab trigger antiviral activity in human hepatoma Hep-G2 cells and enhance the antiviral activity of IFN-gamma in human lung fibroblast A549 cells. Likewise, anti-human-TNF-R1 Ab had antiviral enhancing activity on murine L929 cells engineered to express human TNF-R1. However, L929 cells that express human TNF-R1 lacking most of the intracellular domain fail to respond to anti-human-TNF-R1 Ab. This demonstrates that the intracellular domain of TNF-R1 is necessary to generate antiviral activity. TNF-R1 but not TNF-R2 also signals killing of virus-infected cells by TNF-alpha. Thus, all the known antiviral activities of TNF-alpha are mediated through TNF-R1.
针对两种肿瘤坏死因子受体（TNF受体）即TNF-R1（55千道尔顿）和TNF-R2（75千道尔顿）的激动剂抗体已被证明可介导由肿瘤坏死因子-α（TNF-α）诱导的许多不同功能。我们发现，抗TNF-R1抗体而非抗TNF-R2抗体可在人肝癌Hep-G2细胞中触发抗病毒活性，并增强人肺成纤维细胞A549细胞中干扰素-γ（IFN-γ）的抗病毒活性。同样，抗人TNF-R1抗体对经基因工程改造以表达人TNF-R1的小鼠L929细胞具有抗病毒增强活性。然而，表达缺乏大部分胞内结构域的人TNF-R1的L929细胞对抗人TNF-R1抗体无反应。这表明TNF-R1的胞内结构域对于产生抗病毒活性是必需的。TNF-R1而非TNF-R2也介导TNF-α对病毒感染细胞的杀伤作用。因此，TNF-α的所有已知抗病毒活性均通过TNF-R1介导。
