IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous nitric oxide.

Détails

ID Serval
serval:BIB_16FAD2EE72B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous nitric oxide.
Périodique
Journal of Immunology
Auteur⸱e⸱s
Matthys P., Froyen G., Verdot L., Huang S., Sobis H., Van Damme J., Vray B., Aguet M., Billiau A.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
1995
Volume
155
Numéro
8
Pages
3823-3829
Langue
anglais
Résumé
Mice with a disruption of the IFN-gamma receptor alpha-chain gene (IFN-gamma R alpha o/o mice) were found to be significantly more sensitive than their wild-type counterparts to induction of the anti-CD3-induced disease syndrome. Specifically, when given a selected dose of anti-CD3 Ab, IFN-gamma R alpha o/o mice developed severe hypothermia and hypoglycemia, leading to 100% mortality within 72 h. In contrast, wild-type mice failed to develop overt pathologic manifestations and survived. Histologic examination revealed apoptosis in thymuses and spleens, which were significantly more pronounced in the mutant than in the wild-type mice, as confirmed by flow cytometric and DNA electrophoretic analysis. Apoptosis affected mainly CD4+CD8+ and CD4+CD8- thymocytes. Other histologic alterations were steatosis in livers, and erythrocyte extravasation and infiltration of apoptotic cells in lungs, all of which were exclusively observed in IFN-gamma R alpha o/o mice. Blood levels of TNF, IL-2, IL-6, and IL-10 were slightly more elevated in IFN-gamma R alpha o/o mice, but insufficiently so to explain increased disease severity. Thus, even more elevated cytokine levels in wild-type mice receiving high doses of anti-CD3 Ab were not associated with morbidity or apoptosis. Blood levels of IFN-gamma were barely detectable in anti-CD3-challenged wild-type mice, but were relatively high in the mutant mice. Increased susceptibility of IFN-gamma R alpha o/o mice was associated with impaired nitric oxide (NO) production, as indicated by significantly lower plasma nitrite levels and by more transient expression of spleen inducible NO synthase mRNA. Moreover, treatment of wild-type mice with the NO synthase inhibitor N-nitro-L-arginine methylester resulted in increased anti-CD3-induced morbidity and mortality. The data indicate that IFN-gamma R alpha o/o mice produce less NO and are therefore more sensitive than wild-type mice to the deleterious effect of anti-CD3 Ab.
Mots-clé
Animals, Antibodies/toxicity, Antigens, CD/genetics, Antigens, CD/metabolism, Antigens, CD3/immunology, Apoptosis/immunology, Base Sequence, Cytokines/analysis, Cytokines/secretion, Hypoglycemia/etiology, Hypoglycemia/immunology, Hypothermia/etiology, Hypothermia/immunology, Immunologic Deficiency Syndromes/genetics, Immunologic Deficiency Syndromes/pathology, Lymphocyte Depletion, Mice, Mice, Mutant Strains, Molecular Sequence Data, Nitric Oxide/biosynthesis, Nitric Oxide/blood, Receptors, Interferon/genetics, Receptors, Interferon/metabolism, Spleen, Thymus Gland/pathology
Pubmed
Web of science
Création de la notice
28/01/2008 11:37
Dernière modification de la notice
20/08/2019 12:46
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