Article: article from journal or magazin.
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 of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
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
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