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