Abstract
Gamma delta T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine gamma delta T cells acquire the capacity to differentially produce such cytokines. Splenic gamma delta T cells could be polarized into IFN-gamma- or IL-4-secreting cells in vitro; however, in contrast to CD4+ alpha beta T cells, gamma delta T cells predominantly produced IFN-gamma, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-gamma-producing cells expressed the IL-12 receptor beta 2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed gamma delta T cells also expressed this receptor, even in the absence of IFN-gamma and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed gamma delta T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-gamma by gamma delta T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-gamma by gamma delta T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / immunology
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Cells, Cultured
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Cytokines / biosynthesis
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DNA-Binding Proteins / physiology
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Down-Regulation / immunology*
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GATA3 Transcription Factor
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Interferon-gamma / biosynthesis*
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Interferon-gamma / metabolism
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Interleukin-12 / metabolism
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Interleukin-12 / physiology*
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Interleukin-4 / biosynthesis
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Interleukin-4 / physiology*
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Receptors, Antigen, T-Cell, gamma-delta / metabolism*
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Receptors, Interleukin / antagonists & inhibitors
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Receptors, Interleukin / biosynthesis*
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Receptors, Interleukin-12
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STAT3 Transcription Factor
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STAT4 Transcription Factor
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Trans-Activators / physiology
Substances
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Cytokines
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Interleukin
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Receptors, Interleukin-12
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STAT3 Transcription Factor
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STAT4 Transcription Factor
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Stat3 protein, mouse
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Stat4 protein, mouse
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Trans-Activators
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Interleukin-12
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Interleukin-4
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Interferon-gamma