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Abstract

The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 and 75 kDa. Mutant mice of the invention lacking tumor necrosis factor receptor (TNFR) p55 still express functional TNFRp75 molecules at the cell surface. Normal weight and size of the mutant mice are not altered. Thymocyte development and lymphocyte populations are normal, and clonal deletion of potentially self-reactive T cells is not impaired. Activation of the nuclear transcription factor .kappa.B (NF-.kappa.B), however, is completely abrogated after stimulation with TNF. Moreover, TNFRp55 mutant mice are protected from septic shock induced by bacterial endotoxin or superantigen, but Listeria clearance is severely impaired and mutant mice easily succumb to Listeria infection. Thus, the two TNF receptors are not redundant, are independently controlled, and play different roles in normal and pathological physiology.

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First Claim