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.

Details

Serval ID
serval:BIB_BD95C394475C
Type
Article: article from journal or magazin.
Collection
Publications
Title
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.
Journal
Journal of Immunology
Author(s)
Himmelrich H., Launois P., Maillard I., Biedermann T., Tacchini-Cottier F., Locksley R.M., Röcken M., Louis J.A.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Publication state
Published
Issued date
2000
Volume
164
Number
9
Pages
4819-4825
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
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.
Keywords
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
Create date
24/01/2008 16:08
Last modification date
20/08/2019 16:31
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