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Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder ( gld ) Phenotype
Tumor necrosis factor (TNF) and Fas ligand (FasL) play major roles in the homeostasis of the peripheral immune system. This becomes dramatically obvious in the absence of a functional FasL. Mice with such a deficiency develop a profound lymphadenopathy, splenomegaly, hypergammaglobulinemia, and stra...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195803/ https://www.ncbi.nlm.nih.gov/pubmed/10620607 |
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author | Körner, Heinrich Cretney, Erika Wilhelm, Patricia Kelly, Janice M. Röllinghoff, Martin Sedgwick, Jonathon D. Smyth, Mark J. |
author_facet | Körner, Heinrich Cretney, Erika Wilhelm, Patricia Kelly, Janice M. Röllinghoff, Martin Sedgwick, Jonathon D. Smyth, Mark J. |
author_sort | Körner, Heinrich |
collection | PubMed |
description | Tumor necrosis factor (TNF) and Fas ligand (FasL) play major roles in the homeostasis of the peripheral immune system. This becomes dramatically obvious in the absence of a functional FasL. Mice with such a deficiency develop a profound lymphadenopathy, splenomegaly, hypergammaglobulinemia, and strain-dependent systemic autoimmune disease, and succumb to premature death. It is consequently termed generalized lymphoproliferative disorder (gld). By contrast, TNF deficiency alone does not result in a striking phenotype. Thus, we sought to determine what role TNF might play in contributing to the gld phenotype by creating C57BL/6.gld.TNF(−/−) mice. Contrary to the expected outcome, mice deficient for both FasL and TNF had a substantially milder gld phenotype with regard to mortality, lymphoaccumulation, germinal center formation, and hypergammaglobulinemia. To confirm these data in a strain highly permissive for the phenotype, C3H/HeJ.gld and C3H.HeJ.lpr mice were treated with a TNF-specific monoclonal antibody. This transient neutralization of TNF also resulted in a significantly attenuated lymphoproliferative phenotype. We conclude that TNF is necessary for the full manifestation of the lymphoproliferative disorder, in particular playing a critical role in lymphoaccumulation. Most importantly, absence of TNF protects gld mice against premature death. |
format | Text |
id | pubmed-2195803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21958032008-04-16 Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder ( gld ) Phenotype Körner, Heinrich Cretney, Erika Wilhelm, Patricia Kelly, Janice M. Röllinghoff, Martin Sedgwick, Jonathon D. Smyth, Mark J. J Exp Med Original Article Tumor necrosis factor (TNF) and Fas ligand (FasL) play major roles in the homeostasis of the peripheral immune system. This becomes dramatically obvious in the absence of a functional FasL. Mice with such a deficiency develop a profound lymphadenopathy, splenomegaly, hypergammaglobulinemia, and strain-dependent systemic autoimmune disease, and succumb to premature death. It is consequently termed generalized lymphoproliferative disorder (gld). By contrast, TNF deficiency alone does not result in a striking phenotype. Thus, we sought to determine what role TNF might play in contributing to the gld phenotype by creating C57BL/6.gld.TNF(−/−) mice. Contrary to the expected outcome, mice deficient for both FasL and TNF had a substantially milder gld phenotype with regard to mortality, lymphoaccumulation, germinal center formation, and hypergammaglobulinemia. To confirm these data in a strain highly permissive for the phenotype, C3H/HeJ.gld and C3H.HeJ.lpr mice were treated with a TNF-specific monoclonal antibody. This transient neutralization of TNF also resulted in a significantly attenuated lymphoproliferative phenotype. We conclude that TNF is necessary for the full manifestation of the lymphoproliferative disorder, in particular playing a critical role in lymphoaccumulation. Most importantly, absence of TNF protects gld mice against premature death. The Rockefeller University Press 2000-01-03 /pmc/articles/PMC2195803/ /pubmed/10620607 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Körner, Heinrich Cretney, Erika Wilhelm, Patricia Kelly, Janice M. Röllinghoff, Martin Sedgwick, Jonathon D. Smyth, Mark J. Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder ( gld ) Phenotype |
title | Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder (
gld
) Phenotype
|
title_full | Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder (
gld
) Phenotype
|
title_fullStr | Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder (
gld
) Phenotype
|
title_full_unstemmed | Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder (
gld
) Phenotype
|
title_short | Tumor Necrosis Factor Sustains the Generalized Lymphoproliferative Disorder (
gld
) Phenotype
|
title_sort | tumor necrosis factor sustains the generalized lymphoproliferative disorder (
gld
) phenotype |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195803/ https://www.ncbi.nlm.nih.gov/pubmed/10620607 |
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