Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma.
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.
Vandenabeele
P
P
Laboratory of Molecular Biology, Rijksuniversiteit Gent, Belgium.
Declercq
W
W
Vercammen
D
D
Van de Craen
M
M
Grooten
J
J
Loetscher
H
H
Brockhaus
M
M
Lesslauer
W
W
Fiers
W
W
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology*
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor