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 RIS Download
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