TNF contributes to the immunopathology of perforin/Fas ligand double deficiency

Cretney, Erika, Street, Shayna E. A. and Smyth, Mark J. (2002) TNF contributes to the immunopathology of perforin/Fas ligand double deficiency. Immunology and Cell Biology, 80 5: 436-440. doi:10.1046/j.1440-1711.2002.01108.x

Author Cretney, Erika
Street, Shayna E. A.
Smyth, Mark J.
Title TNF contributes to the immunopathology of perforin/Fas ligand double deficiency
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 2002
Sub-type Article (original research)
DOI 10.1046/j.1440-1711.2002.01108.x
Volume 80
Issue 5
Start page 436
End page 440
Total pages 5
Place of publication London, United Kingdom
Publisher Nature
Language eng
Formatted abstract
Perforin (pfp)/Fas ligand (FasL) double-deficient mice have previously been shown to be infertile, lose weight and die prematurely due to tissue destruction caused by a significant inflammatory infiltrate of monocytes/macrophages and T cells. Herein we have compared disease progression in mice additionally deficient in the inflammatory mediator TNF. Unlike pfp/FasL double-deficient mice (TNF+/+ pfp-/- gld), mice lacking functional TNF, FasL and pfp (TNF-/- pfp-/- gld) were comparatively fertile, with the majority of mice not suffering severe pancreatitis or hysterosalphingitis in the first 5 months of life. The mean lifespan of TNF-/- pfp-/- gld mice was 217 ± 79 days compared with 69 ± 10 days for TNF+/+ pfp-/- gld mice and the majority of moribund TNF-/- pfp-/- gld mice appeared to die as a result of severe pancreatitis, suggesting that loss of TNF was not completely protective. At 8 weeks of age, characteristics associated with the gld phenotype, such as expansion of B220+ CD4- CD8- T cells, lymphadenopathy and hypergammaglobulinemia were comparable between TNF+/+ pfp-/- gld and TNF-/- pfp-/- gld mice, although the lymphoid organs of TNF+/+ pfp-/- gld mice contained greater numbers of B220+ CD4- CD8- T cells, macrophages and T cells. We conclude that TNF is necessary for the full manifestation of immune dysregulation caused by pfp/FasL-deficiency, in particular in the early and overwhelming tissue infiltration and destruction caused by inflammatory cells.
Keyword Apoptosis
Immunodeficiency diseases
Transgenic/ knockout
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

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Created: Mon, 13 Aug 2007, 13:09:24 EST