Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice
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–...
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| Veröffentlicht in: | Nature (London) 1994-12, Vol.372 (6506), p.560-563 |
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| creator | Erickson, Sharon L. de Sauvage, Frederic J. Kikly, Kristine Carver-Moore, Karen Pitts-Meek, Sharon Gillett, Nancy Sheehan, Kathleen C. F. Schreiber, Robert D. Goeddel, David V. Moore, Mark W. |
| description | 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
6,7
; 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 lymphocytes
8,9
. 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. |
| doi_str_mv | 10.1038/372560a0 |
| format | Article |
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6,7
; 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 lymphocytes
8,9
. To clarify the physiological role of TNF-R2, we have generated mice deficient in this receptor by gene targeting. The TNF-R2
−/−
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6,7
; 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 lymphocytes
8,9
. 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.</description><subject>Animals</subject><subject>Antigens, CD</subject><subject>Antigens, Differentiation - metabolism</subject><subject>B-Lymphocytes - cytology</subject><subject>Biological effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cellular biology</subject><subject>Endocrine system</subject><subject>Gene Targeting</subject><subject>Genes</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>letter</subject><subject>Listeriosis - immunology</subject><subject>Lymphocytes</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Necrosis - immunology</subject><subject>Physiology</subject><subject>Receptors, Tumor Necrosis Factor - genetics</subject><subject>Receptors, Tumor Necrosis Factor - metabolism</subject><subject>Receptors, Tumor Necrosis Factor, Type II</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skin - immunology</subject><subject>Skin - pathology</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Thymus Gland - cytology</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU2L1TAUhoMo43UU_ANCcOHHInry0SZZDqOjwqCb67qk6alkaNNrkg7MvzflXhUUdJXF8_DmnPMS8pTDGw7SvJVaNC04uEd2XOmWqdbo-2QHIAwDI9uH5FHONwDQcK3OyJm2FqyEHYnv0Cd0GQeaMeZQwm0od7QstKzzsiYWK19yyHR0viyJ9muhcUmzm-ieeZwmOuAtTsthxlhoiHT_-Yom9HioNhNswDH4sLE5eHxMHoxuyvjk9J6Tr1fv95cf2fWXD58uL66ZV8IWZiU67cdmlG4AiVw77weOVo7C9L6H3gjpuTODGK202retqUs2VvbYa1XhOXl5zD2k5fuKuXRzyNu0LuKy5k4ryVuuhKzmi3-avMZaa6CKz_8Qb-p9Yt2iE6BUwxU0_5OUhXYb7tVR2i6bE47dIYXZpbuOQ7fV2f2ss6rPTnlrP-PwSzz1V_nrI8-VxG-Yfv_3V9YPRdimfw</recordid><startdate>19941208</startdate><enddate>19941208</enddate><creator>Erickson, Sharon L.</creator><creator>de Sauvage, Frederic J.</creator><creator>Kikly, Kristine</creator><creator>Carver-Moore, Karen</creator><creator>Pitts-Meek, Sharon</creator><creator>Gillett, Nancy</creator><creator>Sheehan, Kathleen C. 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F.</au><au>Schreiber, Robert D.</au><au>Goeddel, David V.</au><au>Moore, Mark W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1994-12-08</date><risdate>1994</risdate><volume>372</volume><issue>6506</issue><spage>560</spage><epage>563</epage><pages>560-563</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><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
6,7
; 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 lymphocytes
8,9
. 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>7990930</pmid><doi>10.1038/372560a0</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1994-12, Vol.372 (6506), p.560-563 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743161423 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antigens, CD Antigens, Differentiation - metabolism B-Lymphocytes - cytology Biological effects Cell Differentiation - physiology Cellular biology Endocrine system Gene Targeting Genes Humanities and Social Sciences Humans letter Listeriosis - immunology Lymphocytes Mice multidisciplinary Necrosis - immunology Physiology Receptors, Tumor Necrosis Factor - genetics Receptors, Tumor Necrosis Factor - metabolism Receptors, Tumor Necrosis Factor, Type II Rodents Science Science (multidisciplinary) Skin - immunology Skin - pathology T-Lymphocytes - cytology T-Lymphocytes - metabolism Thymus Gland - cytology Tumor Necrosis Factor-alpha - physiology |
| title | Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice |
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