Abstract
Polymorphisms in TIM-1, a member of the T cell Ig and mucin (TIM) domain family, are associated with relative susceptibility to the development of T helper 2-dominated immune responses such as in allergic asthma. Recent data have also suggested that ligation of TIM-1 can augment T cell activation. We have found that the TIM-1 protein is expressed on CD4(+) T cells in vivo after intranasal immunization. Ectopic expression of TIM-1 during T cell differentiation results in a significant increase in the number of cells producing IL-4 but not IFN-gamma. Furthermore, TIM-1 expression provides a costimulatory signal that increases transcription from the IL-4 promoter and from isolated nuclear factor of activated T cells/activating protein-1 (NFAT/AP-1) elements. Finally, we provide evidence that TIM-1 can be phosphorylated on tyrosine and that TIM-1 costimulation requires its cytoplasmic tail and the conserved tyrosine within that domain. These results constitute evidence that TIM-1 directly couples to phosphotyrosine-dependent intracellular signaling pathways.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intranasal
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Differentiation / genetics
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Cholera Toxin / administration & dosage
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Cholera Toxin / immunology
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Gene Expression Regulation / immunology
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Hepatitis A Virus Cellular Receptor 1
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Humans
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Interferon-gamma / biosynthesis
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Interleukin-4 / biosynthesis
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Jurkat Cells
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Lymphocyte Activation / physiology*
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein Structure, Tertiary
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Transcription, Genetic / immunology
Substances
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Havcr1 protein, mouse
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Hepatitis A Virus Cellular Receptor 1
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Membrane Proteins
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Interleukin-4
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Phosphotyrosine
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Interferon-gamma
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Ovalbumin
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Cholera Toxin