Vandenabeele P, Declercq W, Vercammen D, Van de Craen M, Grooten J, Loetscher H, Brockhaus M, Lesslauer W, Fiers W
Laboratory of Molecular Biology, Rijksuniversiteit Gent, Belgium.
J Exp Med. 1992 Oct 1;176(4):1015-24. doi: 10.1084/jem.176.4.1015.
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.
我们利用肿瘤坏死因子（TNF）在鼠类（m）T细胞系中的反应的物种特异性，研究了人类肿瘤坏死因子p75（hTNF-R75）的生物学作用。TNF对小鼠T细胞的几种介导活性，如细胞因子诱导或增殖，在mTNF和hTNF之间的特异性生物学活性上显示出100至500倍的差异。然而，在大鼠/小鼠T细胞杂交瘤（PC60）中转染hTNF-R75 cDNA后，hTNF特异性生物学活性低100倍的情况转变为与mTNF相同的特异性生物学活性。粒细胞/巨噬细胞集落刺激因子的TNF介导诱导通过添加白细胞介素1而得到强烈协同作用。在后者细胞因子存在的情况下，针对hTNF-R75的配体竞争单克隆抗体（utr-1、utr-2、utr-3）对转染的PC60细胞具有激动作用。通过与羊抗鼠免疫球蛋白抗体交联，这种激动活性进一步增强。这些数据为TNF-R75在T细胞中诱导细胞因子分泌中的功能作用提供了直接证据，且不涉及依赖配体的TNF-R55。
