TY - JOUR
T1 - Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice
AU - Erickson, Sharon L.
AU - De Sauvage, Frederic J.
AU - Kikly, Kristine
AU - Carver-Moore, Karen
AU - Pitts-Meek, Sharon
AU - Gillett, Nancy
AU - Sheehan, Kathleen C.F.
AU - Schreiber, Robert D.
AU - Goeddel, David V.
AU - Moore, Mark W.
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028063303&partnerID=8YFLogxK
U2 - 10.1038/372560a0
DO - 10.1038/372560a0
M3 - Article
C2 - 7990930
AN - SCOPUS:0028063303
SN - 0028-0836
VL - 372
SP - 560
EP - 563
JO - Nature
JF - Nature
IS - 6506
ER -