GATA-3 regulates the development and function of invariant NKT cells

J Immunol. 2006 Nov 15;177(10):6650-9. doi: 10.4049/jimmunol.177.10.6650.

Abstract

Although invariant NKT (iNKT) cells participate in many aspects of immune responses, the molecular mechanisms regulating their development, maturation, and activation are still poorly understood. GATA-3 is a T cell-specific transcription factor that is also expressed in iNKT cells. The critical role of GATA-3 in conventional alphabeta T cells has been well documented, but whether GATA-3 also regulates the development and function of iNKT cells is unknown. In the present study, we report that deficiency of GATA-3 results in cell-intrinsic defects in the thymic development and peripheral maturation of murine iNKT cells. In addition, GATA-3 is also required for survival, activation, and effector functions of this unique population of T cells. Our data also reveal a previously unidentified peripheral maturation step that is GATA-3 dependent.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cytokines / biosynthesis
  • Cytokines / blood
  • GATA3 Transcription Factor / biosynthesis
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / physiology*
  • Galactosylceramides / administration & dosage
  • Injections, Intravenous
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • Galactosylceramides
  • Gata3 protein, mouse
  • Receptors, Antigen, T-Cell
  • alpha-galactosylceramide
  • Interferon-gamma