The IL-4 rapidly produced in BALB/c mice after infection with Leishmania major down-regulates IL-12 receptor beta 2-chain expression on CD4+ T cells resulting in a state of unresponsiveness to IL-12.

Détails

ID Serval
serval:BIB_C6396D568EF9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The IL-4 rapidly produced in BALB/c mice after infection with Leishmania major down-regulates IL-12 receptor beta 2-chain expression on CD4+ T cells resulting in a state of unresponsiveness to IL-12.
Périodique
Journal of Immunology
Auteur(s)
Himmelrich H., Parra-Lopez C., Tacchini-Cottier F., Louis J.A., Launois P.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
1998
Volume
161
Numéro
11
Pages
6156-6163
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Within 1 day of infection with Leishmania major, susceptible BALB/c mice produce a burst of IL-4 in their draining lymph nodes, resulting in a state of unresponsiveness to IL-12 in parasite-specific CD4+ T cells within 48 h. In this report we examined the molecular mechanism underlying this IL-12 unresponsiveness. Extinction of IL-12 signaling in BALB/c mice is due to a rapid down-regulation of IL-12R beta2-chain mRNA expression in CD4+ T cells. In contrast, IL-12R beta2-chain mRNA expression was maintained on CD4+ T cells from resistant C57BL/6 mice. The down-regulation of the IL-12R beta2-chain mRNA expression in BALB/c CD4+ T cells is a consequence of the early IL-4 production. In this murine model of infection, a strict correlation is shown in vivo between expression of the IL-12R beta2-chain in CD4+ T cells and the development of a Th1 response and down-regulation of the mRNA beta2-chain expression and the maturation of a Th2 response. Treatment of BALB/c mice with IFN-gamma, even when IL-4 has been produced for 48 h, resulted in maintenance of IL-12R beta2-chain mRNA expression and IL-12 responsiveness. The data presented here support the hypothesis that the genetically determined susceptibility of BALB/c mice to infection with L. major is primarily based on an up-regulation of IL-4 production, which secondarily induces extinction of IL-12 signaling.
Mots-clé
Animals, CD4-Positive T-Lymphocytes/metabolism, Down-Regulation/immunology, Female, Immune Tolerance, Injections, Intraperitoneal, Interferon-gamma/administration & dosage, Interferon-gamma/physiology, Interleukin-4/biosynthesis, Interleukin-4/physiology, Leishmania major/immunology, Leishmaniasis, Cutaneous/immunology, Leishmaniasis, Cutaneous/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, RNA, Messenger/antagonists & inhibitors, RNA, Messenger/biosynthesis, Receptors, Interleukin/administration & dosage, Receptors, Interleukin/biosynthesis, Receptors, Interleukin-12, Th2 Cells/metabolism, Transcription, Genetic/immunology
Pubmed
Web of science
Création de la notice
24/01/2008 16:08
Dernière modification de la notice
03/03/2018 21:17
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