The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor

Matthias Grell, Eleni Douni, Harald Wajant, Matthias Löhden, Matthias Clauss, Beate Maxeiner, Spiros Georgopoulos, Werner Lesslauer, George Kollias, Klaus Pfizenmaier, Peter Scheurich

Research output: Contribution to journalArticle

1038 Scopus citations

Abstract

The 60 kDa tumor necrosis factor receptor (TNFR60) is regarded as the major signal transducer of TNF-induced cellular responses, whereas the signal capacity and role of the 80 kDa TNFR (TNFR80) remain largely undefined. We show here that the transmembrane form of TNF is superior to soluble TNF in activating TNFR80 in various systems such as T cell activation, thymocyte proliferation, and granulocyte/macrophage colony-stimulating factor production. Intriguingly, activation of TNFR80 by membrane TNF can lead to qualitatively different TNF responses such as rendering resistant tumor cells sensitive to TNF-mediated cytotoxicity. This study demonstrates that the diversity of TNF effects can be controlled through the differential sensitivity of TNFR80 for the two forms of TNF and suggests an important physiological role for TNFR80 in local inflammatory responses.

Original languageEnglish (US)
Pages (from-to)793-802
Number of pages10
JournalCell
Volume83
Issue number5
DOIs
StatePublished - Dec 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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