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.
- Launois P World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Lausanne, Switzerland.
- Gumy A
- Himmelrich H
- Locksley RM
- Röcken M
- Louis JA
- 2002-04-24
Published in:
- Journal of immunology (Baltimore, Md. : 1950). - 2002
Animals
Antibodies
Antigens, Protozoan
CD4-Positive T-Lymphocytes
Cell Differentiation
Cells, Cultured
Cytokines
Disease Progression
Female
Interferon-gamma
Interleukin-12
Interleukin-4
Kinetics
Leishmania major
Leishmaniasis, Cutaneous
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Protozoan Proteins
RNA, Messenger
Receptors, Antigen, T-Cell, alpha-beta
Th2 Cells
English
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.4049/jimmunol.168.9.4628
- PMID 11971011
- Persistent URL
- https://sonar.ch/global/documents/277858
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