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Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells.

Signal transducers and activators of transcription (STATs) are activated by tyrosine phosphorylation in response to cytokines and mediate many of their functional responses. Stat4 was initially cloned as a result of its homology with Stat1 (refs 4, 5) and is widely expressed, although it is only tyrosine-phosphorylated after stimulation of T cells with interleukin (IL)-12 (refs 6,7). IL-12 is required for the T-cell-independent induction of the cytokine interferon (IFN)-gamma, a key step in the initial suppression of bacterial and parasitic infections. IL-12 is also important for the development of a Th1 response, which is critical for effective host defence against intracellular pathogens. To determine the function of Stat4 and its role in IL-12 signalling, we have produced mice that lack Stat4 by gene targeting. The mice were viable and fertile, with no detectable defects in haematopoiesis. However, all IL-12 functions tested were disrupted, including the induction of IFN-gamma, mitogenesis, enhancement of natural killer cytolytic function and Th1 differentiation.

Pubmed ID: 8700208


  • Thierfelder WE
  • van Deursen JM
  • Yamamoto K
  • Tripp RA
  • Sarawar SR
  • Carson RT
  • Sangster MY
  • Vignali DA
  • Doherty PC
  • Grosveld GC
  • Ihle JN



Publication Data

July 11, 1996

Associated Grants


Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular
  • Cytotoxicity, Immunologic
  • DNA-Binding Proteins
  • Gene Targeting
  • Interferon-gamma
  • Interleukin-12
  • Killer Cells, Natural
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • STAT4 Transcription Factor
  • Signal Transduction
  • Spermatogenesis
  • Spleen
  • T-Lymphocytes
  • Trans-Activators