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

Nature. 1994 Dec 8;372(6506):560-3. doi: 10.1038/372560a0.


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.

MeSH terms

  • Animals
  • Antigens, CD*
  • Antigens, Differentiation / metabolism
  • B-Lymphocytes / cytology
  • Cell Differentiation / physiology
  • Gene Targeting
  • Humans
  • Listeriosis / immunology
  • Mice
  • Necrosis / immunology
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type II
  • Skin / immunology
  • Skin / pathology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Tumor Necrosis Factor-alpha / physiology*


  • Antigens, CD
  • Antigens, Differentiation
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha