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Tumor necrosis factor sustains the generalized lymphoproliferative disorder (gld) phenotype

Citation

Korner, H and Cretney, E and Wilhelm, P and Kelly, JM and Rollinghoff, M and Sedgwick, JD and Smyth, MJ, Tumor necrosis factor sustains the generalized lymphoproliferative disorder (gld) phenotype, The Journal of Experimental Medicine, 191, (1) pp. 89-96. ISSN 0022-1007 (2000) [Refereed Article]

DOI: doi:10.1084/jem.191.1.89

Abstract

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-specipic 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Korner, H (Professor Heinrich Korner)
ID Code:72460
Year Published:2000
Web of Science® Times Cited:47
Deposited By:Research Division
Deposited On:2011-08-26
Last Modified:2011-08-29
Downloads:0

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