Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice

Sharon L. Erickson, Frederic J. De Sauvage, Kristine Kikly, Karen Carver-Moore, Sharon Pitts-Meek, Nancy Gillett, Kathleen C.F. Sheehan, Robert D. Schreiber, David V. Goeddel, Mark W. Moore

Research output: Contribution to journalArticlepeer-review

558 Scopus citations

Abstract

TUMOUR necrosis factor (TNF) elicits multiple biological effects through two distinct cell surface receptors, TNF-R1 (p55) and TNF-R2 (p75). Most TNF-mediated biological responses, such as cell death, gene induction, antiviral activity and cytokine production, have been attributed to TNF-R1 (refs 1-5). Gene targeting of this receptor confirms its role in the lethality attributable to low doses of lipopolysaccharide after sensitization with D-galactosamine6,7; surprisingly, the toxicity of high doses of lipopolysaccharide was unaffected. The function of TNF-R2 is less well understood, although there are data supporting a role in T-cell development and the proliferation of cytotoxic T lymphocytes8,9. To clarify the physiological role of TNF-R2, we have generated mice deficient in this receptor by gene targeting. The TNF-R2-/- mice show normal T-cell development and activity, but we find that they have increased resistance to TNF-induced death. Additionally, such mice injected subcutaneously with TNF show a dramatic decrease in tissue necrosis, indicating that this receptor plays a role in the necrotic effects of TNF.

Original languageEnglish
Pages (from-to)560-563
Number of pages4
JournalNature
Volume372
Issue number6506
DOIs
StatePublished - Jan 1 1994

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