The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor.
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.
Institute of Cell Biology and Immunology, University of Stuttgart, Federal Republic of Germany.
M
M
Grell
E
E
Douni
H
H
Wajant
M
M
Löhden
M
M
Clauss
B
B
Maxeiner
S
S
Georgopoulos
W
W
Lesslauer
G
G
Kollias
K
K
Pfizenmaier
P
P
Scheurich
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D016466:CHO Cells; D002455:Cell Division; D002462:Cell Membrane; D002478:Cells, Cultured; D018920:Coculture Techniques; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor