Document Detail


CD137-deficient mice have reduced NK/NKT cell numbers and function, are resistant to lipopolysaccharide-induced shock syndromes, and have lower IL-4 responses.
MedLine Citation:
PMID:  15356173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD137, a member of the TNF superfamily, is involved in T cell and NK cell activation and cytokine production. To establish its in vivo role in systems dependent on NK and NKT cells, we studied the response of CD137-/- mice to LPS-induced shock, tumor killing, and their IL-4-controlled Th2 responses. In both high and low dose shock models, all the CD137-deficient mice, but none of the wild-type BALB/c mice, survived. After injection of LPS/2-amino-2-deoxy-D-galactose (D-gal), CD137-/- mice had reduced serum cytokine levels and substantially impaired liver IFN-gamma and TNF-alpha mRNA levels. Phenotypic analysis of mononuclear cells revealed fewer NK and NKT cells in the CD137-/- mice. The knockout mice did not generate a rapid IL-4 response after systemic T cell activation, or effective Ag-specific Th2 responses. In addition, both in vitro and in vivo NK-specific cytolytic activities were reduced. These findings suggest that CD137-directed NK/NKT cells play an important role in the inflammatory response leading to the production of proinflammatory cytokines, LPS-induced septic shock, and tumor killing, as well as IL-4-dependent Th2 responses.
Authors:
Dass S Vinay; Beom K Choi; Jun S Bae; Won Y Kim; Bryan M Gebhardt; Byoung S Kwon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  173     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-09     Completed Date:  2004-10-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4218-29     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2004 The American Association of Immunologists, Inc.
Affiliation:
Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
4-1BB Ligand
Animals
Antibodies, Blocking / pharmacology
Antigens, CD
Antigens, CD137
Cell Line, Tumor
Cells, Cultured
Cytotoxicity, Immunologic / genetics
Drug-Induced Liver Injury / genetics,  immunology,  pathology
Immunity, Innate / genetics
Interferon-gamma / antagonists & inhibitors,  biosynthesis,  genetics
Interleukin-4 / antagonists & inhibitors,  physiology*,  secretion
Killer Cells, Natural / immunology*,  metabolism,  pathology
Ligands
Lipopolysaccharides / toxicity*
Lymphocyte Count
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Receptors, Nerve Growth Factor / antagonists & inhibitors,  deficiency*,  genetics*,  physiology
Receptors, Tumor Necrosis Factor / antagonists & inhibitors,  deficiency*,  genetics*,  physiology
Shock, Septic / genetics*,  immunology*,  pathology,  prevention & control
Signal Transduction / genetics,  immunology
Syndrome
T-Lymphocyte Subsets / immunology*,  metabolism,  pathology
Th2 Cells / immunology,  metabolism
Tumor Necrosis Factor-alpha / antagonists & inhibitors,  immunology,  physiology
Grant Support
ID/Acronym/Agency:
P30EY002377/EY/NEI NIH HHS; R01EY013325/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/4-1BB Ligand; 0/Antibodies, Blocking; 0/Antigens, CD; 0/Antigens, CD137; 0/Ligands; 0/Lipopolysaccharides; 0/Receptors, Nerve Growth Factor; 0/Receptors, Tumor Necrosis Factor; 0/Tnfrsf9 protein, mouse; 0/Tnfsf9 protein, mouse; 0/Tumor Necrosis Factor-alpha; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma

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