title: Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice.
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-galactosamine; 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 lymphocytes. 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.
authors.affiliation: Department of Cell Genetics, Genentech, South San Francisco, California 94080.
authors.forename: S L
authors.initials: SL
authors.lastname: Erickson
authors.forename: F J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: K
authors.initials: K
authors.lastname: Kikly
authors.forename: K
authors.initials: K
authors.lastname: Carver-Moore
authors.forename: S
authors.initials: S
authors.lastname: Pitts-Meek
authors.forename: N
authors.initials: N
authors.lastname: Gillett
authors.forename: K C
authors.initials: KC
authors.lastname: Sheehan
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: D V
authors.initials: DV
authors.lastname: Goeddel
authors.forename: M W
authors.initials: MW
authors.lastname: Moore
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D018390:Gene Targeting; D006801:Humans; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D009336:Necrosis / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha