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

W. E. Thierfelder, J. M. Van Deursen, K. Yamamoto, R. A. Tripp, S. R. Sarawar, R. T. Carson, M. Y. Sangster, D. A.A. Vignali, P. C. Doherty, G. C. Grosveld, J. N. Ihle

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Abstract

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)-γ, 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-γ, mitogenesis, enhancement of natural killer cytolytic function and Th1 differentiation.

Original languageEnglish (US)
Pages (from-to)171-174
Number of pages4
JournalNature
Volume382
Issue number6587
DOIs
StatePublished - Aug 2 1996

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    Thierfelder, W. E., Van Deursen, J. M., Yamamoto, K., Tripp, R. A., Sarawar, S. R., Carson, R. T., Sangster, M. Y., Vignali, D. A. A., Doherty, P. C., Grosveld, G. C., & Ihle, J. N. (1996). Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature, 382(6587), 171-174. https://doi.org/10.1038/382171a0