Abstract
IL-12 is a novel heterodimeric cytokine important for the regulation and differentiation of lymphocytes and NK cells. Like other cytokines, IL-12 mediates its biologic activity through high-affinity receptors expressed on responsive cells. To date, a large number of receptors for IL-12 have been found only on PBMC following activation with PHA or IL-2. To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway in cytotoxic T cells, we studied a number of human T cell lines that had been transformed to permanent growth with Herpesvirus saimiri, an oncogenic virus of nonhuman primates. This paper reports the expression of IL-12R on a human gamma delta T cell line that responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin. Using these T cells as a model of IL-12 signal transduction, we confirmed that these events involve members of the Janus kinase family of nonreceptor tyrosine kinases JAK2, TYK2, and signal transducer and activator of transcription 4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Transformed
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Cell Transformation, Viral
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Cytotoxicity, Immunologic / drug effects
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DNA-Binding Proteins / metabolism
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Herpesvirus 2, Saimiriine / physiology*
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Humans
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Interleukin-12 / pharmacology*
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Interleukin-2 / pharmacology
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Janus Kinase 2
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Janus Kinase 3
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Lymphocyte Activation / drug effects*
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism
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Proto-Oncogene Proteins*
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Receptors, Antigen, T-Cell, gamma-delta / immunology*
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STAT4 Transcription Factor
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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T-Lymphocytes / virology
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TYK2 Kinase
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Trans-Activators / metabolism
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Tyrosine / metabolism
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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DNA-Binding Proteins
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Interleukin-2
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Proteins
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell, gamma-delta
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STAT4 Transcription Factor
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STAT4 protein, human
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Trans-Activators
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Interleukin-12
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Tyrosine
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Protein-Tyrosine Kinases
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JAK2 protein, human
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JAK3 protein, human
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Janus Kinase 2
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Janus Kinase 3
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TYK2 Kinase
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TYK2 protein, human