Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at the onset of infection with Leishmania major instructs Th2 cell development, resulting in nonhealing lesions.

Details

Serval ID
serval:BIB_C2FB84A64E87
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at the onset of infection with Leishmania major instructs Th2 cell development, resulting in nonhealing lesions.
Journal
Journal of Immunology
Author(s)
Launois P., Gumy A., Himmelrich H., Locksley R.M., Röcken M., Louis J.A.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Publication state
Published
Issued date
2002
Volume
168
Number
9
Pages
4628-4635
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Rapid production of IL-4 by Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4(+) T cells expressing the V beta 4-V alpha 8 TCR chains has been shown to drive aberrant Th2 cell development and susceptibility to Leishmania major in BALB/c mice. In contrast, mice from resistant strains fail to express this early IL-4 response. However, administration of either anti-IL-12 or -IFN-gamma at the initiation of infection allows the expression of this early IL-4 response in resistant mice. In this work we show that Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells also expressing the V beta 4-V alpha 8 TCR chains are the source of the early IL-4 response to L. major in resistant mice given anti-IL-12 or -IFN-gamma Abs only at the onset of infection. Strikingly, these cells were found to be required for the reversal of the natural resistance of C57BL/6 mice following a single administration of anti-IL-12 or -IFN-gamma Abs. Together these results suggest that a deficiency in mechanisms capable of down-regulating the early IL-4 response to L. major contributes to the exquisite susceptibility of BALB/c mice to L. major.
Keywords
Animals, Antibodies/pharmacology, Antigens, Protozoan, CD4-Positive T-Lymphocytes/immunology, Cell Differentiation, Cells, Cultured, Cytokines/antagonists & inhibitors, Disease Progression, Female, Interferon-gamma/antagonists & inhibitors, Interferon-gamma/immunology, Interleukin-12/antagonists & inhibitors, Interleukin-12/immunology, Interleukin-4/biosynthesis, Interleukin-4/genetics, Kinetics, Leishmania major, Leishmaniasis, Cutaneous/immunology, Leishmaniasis, Cutaneous/pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Protozoan Proteins/pharmacology, RNA, Messenger/biosynthesis, Receptors, Antigen, T-Cell, alpha-beta/analysis, Receptors, Antigen, T-Cell, alpha-beta/genetics, Th2 Cells/immunology
Pubmed
Web of science
Create date
28/01/2008 11:06
Last modification date
20/08/2019 15:38
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