Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma
Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma
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转染的大鼠/小鼠 T 细胞杂交瘤中人肿瘤坏死因子受体 p75 的功能表征
DOI：
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发表时间：
1992
影响因子：
15.3
通讯作者：
W. Fiers
中科院分区：
文献类型：
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作者：
Peter Vandenabeele;W. Declercq;D. Vercammen;M. V. D. Craen;J. Grooten;H. Loetscher;M. Brockhaus;W. Lesslauer;W. Fiers
我们利用小鼠(M)T细胞系中肿瘤坏死因子反应的种属特异性，研究了人肿瘤坏死因子p75(hTNF-R75)的生物学作用。几种肿瘤坏死因子介导的小鼠T细胞活性，如细胞因子的诱导或增殖，在比生物活性方面，mtnf和hTNF显示出100-500倍的差异。然而，在大鼠/小鼠T细胞杂交瘤(PC60)中转染人肿瘤坏死因子-R75基因后，hTNF的比活性由原来的100倍转变为与mtnf相同的比活性。IL-1对肿瘤坏死因子介导的粒细胞/巨噬细胞集落刺激因子的诱导有很强的协同作用。在后者的存在下，针对hTNF-R75的配基竞争的单抗(UTR-1、UTR-2、UTR-3)在转染的PC60细胞上被激动化。通过与绵羊抗鼠免疫球蛋白抗体进行交联，这种激动剂的活性进一步增强。这些数据为肿瘤坏死因子-R75在T细胞分泌细胞因子中的功能作用提供了直接证据，而不涉及配体依赖的肿瘤坏死因子-R55。
We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500- fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.