Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice.

Details

Serval ID
serval:BIB_ACA8DE56896E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice.
Journal
International Immunology
Author(s)
Eugster H.P., Muller M., Karrer U., Car B.D., Schnyder B., Eng V.M., Woerly G., Le Hir M., di Padova F., Aguet M., Zinkernagel R., Bluethmann H., Ryffel B.
ISSN
0953-8178 (Print)
ISSN-L
0953-8178
Publication state
Published
Issued date
1996
Volume
8
Number
1
Pages
23-36
Language
english
Abstract
To investigate the roles of tumor necrosis factor (TNF) and lymphotoxin (LT)-alpha in the development and function of the immune system, the Tnf and Ltalpha genes were simultaneously inactivated in mice by homologous recombination. These mutant mice are highly susceptible to Listeria monocytogenes infection and resistant to endotoxic shock induced by the combined administration of D-galactosamine (D-GaIN) and lipopolysaccharide (LPS). Their splenic microarchitecture is disorganized, characterized by the loss of the clearly defined marginal zone, ill defined T and B cell areas, and absence of MAdCAM-1 and reduced ICAM-1, VCAM-1 and Mac-1 expression. They are devoid of peripheral lymph nodes and Peyer's patches, and show a strong reduction of IgA+ plasma cells in the intestinal lamina propria. The alymphoplasia is accompanied by a marked B lymphocytosis and reduced basal lg levels. Ig depositions in the renal glomerulus and a strong up-regulation of MHC class I antigen expression on endothelial cells of different tissues are observed. The primary humoral immune response towards sheep red blood cells reveals a defective IgG isotype switch, while that against vesicular stomatitis virus is normal. The cytotoxic T cell responses are attenuated, although still effective, against vaccinia, lymphocytic choriomeningitis virus (LCMV-ARM) and LCMV-WE. In conclusion, the combined inactivation of Tnf and Ltalpha confirms their essential role in the normal development and function of the immune system.
Keywords
Animals, Antibody Formation, B-Lymphocytes/immunology, Base Sequence, Immunity, Immunoglobulin Isotypes/analysis, Intestines/immunology, Listeriosis/immunology, Liver/immunology, Lymphocyte Count, Lymphocytic Choriomeningitis/immunology, Lymphotoxin-alpha/genetics, Lymphotoxin-alpha/immunology, Mice, Mice, Mutant Strains, Molecular Sequence Data, Mycobacterium Infections/immunology, Spleen/immunology, T-Lymphocytes, Cytotoxic/immunology, Thymus Gland/immunology, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/immunology
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:36
Last modification date
20/08/2019 15:16
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