TNF Receptor Involvement in TNF-Mediated Activities against Syngeneic Malignant and Normal Mouse Thymocytes

Receptor-dependent tumor necrosis factor (TNF)-mediated activities against mouse thymoma cells and normal thymocytes syngeneic for C57 mice were examined to determine the specific involvement of TNF receptors R1 and R2. Both receptors are expressed by EL4 thymoma cells and normal C57 thymocytes. TNF-mediated activities included (a) cytotoxicity, (b) induction of hyposensitivity to TNF-mediated lysis, (c) costimulatory stimulation of thymocyte proliferation, and (d) activation of NF-kB-like transcription factor. The ability of polyclonal antisera against TNF receptors to mimic the above TNF-mediated activities was determined. The results clearly showed that anti-TNF-R1 antibodies were cytotoxic against EL4 cells, induced hyposensitivity of S-EL4 to TNF lysis and activated the NF-kB-like transcription factor in EL4 cells and syngeneic normal thymocytes. Antisera against TNF-R2 only mimicked TNF-mediated costimulation of thymocyte proliferation with IL2. No direct correlation was noted between TNF activation of NF-kB and TINF-mediated lysis.