Cutting edge: granulocyte-macrophage colony-stimulating factor is the major CD8+ T cell-derived licensing factor for dendritic cell activation

J Immunol. 2010 May 1;184(9):4625-9. doi: 10.4049/jimmunol.0903873. Epub 2010 Mar 31.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Communication / immunology
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / metabolism
  • Cytokines / physiology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • 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

Substances

  • Cytokines
  • Inflammation Mediators
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • TCF Transcription Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor