Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny

Immunity. 2006 Sep;25(3):487-97. doi: 10.1016/j.immuni.2006.06.017. Epub 2006 Aug 31.


Invariant natural killer T (iNKT) cell-derived cytokines have important functions in inflammation, host defense, and immunoregulation. Yet, when and how iNKT cells undergo effector differentiation, which endows them with the capacity to rapidly secrete cytokines upon activation, remains unknown. We discovered that granulocyte-macrophage colony-stimulating factor (Csf-2)-deficient mice developed iNKT cells that failed to respond to the model antigen alpha-galactosylceramide because of an intrinsic defect in the fusion of secretory vesicles with the plasma membrane. Exogenous Csf-2 corrected the functional defect only when supplied during the development of thymic, but not mature, splenic Csf-2-deficient iNKT cells. Thus, we ascribe a unique function to Csf-2, which regulates iNKT cell effector differentiation during development by a mechanism that renders them competent for cytokine secretion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Humans
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / physiology
  • Receptor, Macrophage Colony-Stimulating Factor / biosynthesis
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • Cytokines
  • NF-kappa B
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor