In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.
Détails
ID Serval
serval:BIB_BD95C394475C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.
Périodique
Journal of Immunology
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2000
Volume
164
Numéro
9
Pages
4819-4825
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Résumé
In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vbeta4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vbeta4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vbeta4 Valpha8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vbeta4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vbeta4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vbeta4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.
Mots-clé
Animals, CD4-Positive T-Lymphocytes/metabolism, CD4-Positive T-Lymphocytes/pathology, Cell Differentiation/genetics, Cell Differentiation/immunology, Disease Progression, Down-Regulation/immunology, Female, Immune Tolerance/genetics, Immunity, Innate/genetics, Injections, Intraperitoneal, Interleukin-12/metabolism, Interleukin-12/pharmacology, Interleukin-4/administration & dosage, Interleukin-4/biosynthesis, Leishmania major/immunology, Leishmaniasis, Cutaneous/genetics, Leishmaniasis, Cutaneous/immunology, Lymph Nodes/cytology, Lymph Nodes/immunology, Lymphopenia/genetics, Lymphopenia/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Interleukin/antagonists & inhibitors, Receptors, Interleukin/biosynthesis, Receptors, Interleukin-12, Th2 Cells/immunology, Th2 Cells/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 16:08
Dernière modification de la notice
20/08/2019 16:31