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J Immunol ; 184(9): 4625-9, 2010 May 01.
Article in English | MEDLINE | ID: mdl-20357255

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Differentiation/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/physiology , Animals , Cell Communication/immunology , Cell Proliferation , Cells, Cultured , Coculture Techniques , Cytokines/metabolism , Cytokines/physiology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Inflammation Mediators/metabolism , Inflammation Mediators/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/deficiency , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , TCF Transcription Factors/metabolism , TCF Transcription Factors/physiology , Up-Regulation/immunology
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