Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-12-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0953-8178
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-36
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8671586-Animals, pubmed-meshheading:8671586-Antibody Formation, pubmed-meshheading:8671586-B-Lymphocytes, pubmed-meshheading:8671586-Base Sequence, pubmed-meshheading:8671586-Immunity, pubmed-meshheading:8671586-Immunoglobulin Isotypes, pubmed-meshheading:8671586-Intestines, pubmed-meshheading:8671586-Listeriosis, pubmed-meshheading:8671586-Liver, pubmed-meshheading:8671586-Lymphocyte Count, pubmed-meshheading:8671586-Lymphocytic Choriomeningitis, pubmed-meshheading:8671586-Lymphotoxin-alpha, pubmed-meshheading:8671586-Mice, pubmed-meshheading:8671586-Mice, Mutant Strains, pubmed-meshheading:8671586-Molecular Sequence Data, pubmed-meshheading:8671586-Mycobacterium Infections, pubmed-meshheading:8671586-Spleen, pubmed-meshheading:8671586-T-Lymphocytes, Cytotoxic, pubmed-meshheading:8671586-Thymus Gland, pubmed-meshheading:8671586-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice.
pubmed:affiliation
Swiss Federal Institute of Technology, Institute of Toxicology, Schorenstasse 16, 8603 Schwerzenbach, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't