GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation

Immunity. 2003 Jul;19(1):83-94. doi: 10.1016/s1074-7613(03)00176-6.

Abstract

GATA-3 is expressed at higher levels in CD4 than in CD8 SP thymocytes. Here we show that upregulation of GATA-3 expression in DP thymocytes is triggered by TCR stimulation, and the extent of upregulation correlates with the strength of the TCR signal. Overexpression of GATA-3 or a partial GATA-3 agonist during positive selection inhibits CD8 SP cell development but is not sufficient to divert class I-restricted T cell precursors to the CD4 lineage. Conversely, expression of the GATA-3 antagonist ROG or of a GATA-3 siRNA hairpin markedly enhances development of CD8 SP cells and reduces CD4 SP development. We propose that GATA-3 contributes to linking the TCR signal strength to the differentiation program of CD4 and CD8 thymocytes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Differentiation
  • Cell Lineage
  • DNA-Binding Proteins / physiology*
  • GATA3 Transcription Factor
  • Mice
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • Receptors, Antigen, T-Cell / physiology*
  • Thymus Gland / cytology
  • Trans-Activators / physiology*

Substances

  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Receptors, Antigen, T-Cell
  • Trans-Activators