Abstract
During priming, CD8(+) T lymphocytes can induce robust maturation of dendritic cells (DCs) in a CD40-independent manner by secreting licensing factor(s). In this study, we isolate this so-far elusive licensing factor and identify it, surprisingly, as GM-CSF. This provides a new face for an old factor with a well-known supporting role in DC development and recruitment. Signaling through the GM-CSFR in ex vivo-purified DCs upregulated the expression of costimulatory molecules more efficiently than did any tested TLR agonist and provided a positive feedback loop in the stimulation of CD8(+) T cell proliferation. Combined with a variety of microbial stimuli, GM-CSF supports the formation of potent "effector" DCs capable of secreting a variety of proinflammatory cytokines that guide the differentiation of T cells during the immune response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Communication / immunology
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Cell Differentiation / immunology*
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Cell Proliferation
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Cells, Cultured
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Coculture Techniques
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Cytokines / metabolism
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Cytokines / physiology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
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Inflammation Mediators / metabolism
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Inflammation Mediators / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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TCF Transcription Factors / metabolism
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TCF Transcription Factors / physiology
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Up-Regulation / immunology
Substances
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Cytokines
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Inflammation Mediators
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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TCF Transcription Factors
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Granulocyte-Macrophage Colony-Stimulating Factor