Details

Autor(en) / Beteiligte

• Thierfelder, William E
• van Deursen, Jan M
• Yamamoto, Koh
• Tripp, Ralph A
• Sarawar, Sally R
• Carson, Richard T
• Sangster, Mark Y
• Vignali, Dario A. A
• Doherty, Peter C
• Grosveld, Gerard C
• Ihle, James N

Titel

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

Ist Teil von

• Nature (London), 1996-07, Vol.382 (6587), p.171-174

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.