Abstract
An efficient Th1-driven adaptive immune response requires activation of the T cell receptor and secretion of the T cell stimulatory cytokine IL-12 by activated antigen-presenting cells. IL-12 triggers Th1 polarization of naive CD4(+) T cells and secretion of IFN-gamma. We describe a new heterodimeric cytokine termed IL-27 that consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide. IL-27 is an early product of activated antigen-presenting cells and drives rapid clonal expansion of naive but not memory CD4(+) T cells. It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigen-Presenting Cells / metabolism
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CD4-Positive T-Lymphocytes / physiology*
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Carrier Proteins / analysis*
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Cell Division
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Dimerization
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Glutathione Transferase*
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Glycoproteins / analysis*
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Interferon-gamma / biosynthesis
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Interleukin-12 / physiology
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Interleukins / chemistry
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Interleukins / physiology*
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Minor Histocompatibility Antigens
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Molecular Sequence Data
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Protein Conformation
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Receptors, Cytokine / metabolism
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Receptors, Interleukin
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Sequence Alignment
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Th1 Cells / immunology*
Substances
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Carrier Proteins
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EBI3 protein, human
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Glycoproteins
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Gsto1 protein, mouse
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Il27 protein, mouse
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Il27ra protein, mouse
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Interleukins
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Minor Histocompatibility Antigens
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Receptors, Cytokine
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Receptors, Interleukin
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Interleukin-12
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Interferon-gamma
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Glutathione Transferase