Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells (original) (raw)

Nature volume 382, pages 171–174 (1996)Cite this article

Abstract

SIGNAL transducers and activators of transcription (STATs) are activated by tyrosine phosphorylation in response to cytokines and mediate many of their functional responses1–3. Stat4 was initially cloned as a result of its homology with Statl (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 Thl response, which is critical for effective host defence against intracellular pathogens8,9. 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 haemato-poiesis. However, all IL-12 functions tested were disrupted, including the induction of IFN-γ, mitogenesis, enhancement of natural killer cytolytic function and Thl differentiation.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Ihle, J. N. Nature 377, 591–594 (1995).
    Article ADS CAS Google Scholar
  2. Ihle, J. N. Cell 84, 331–334 (1996).
    Article CAS Google Scholar
  3. Schindler, C. & Darnell, J. E. Jr A. Rev. Biochem. 64, 621–651 (1995).
    Article CAS Google Scholar
  4. Yamamoto, K. et al. Molec. cell. Biol. 14, 4342–4349 (1994).
    Article CAS Google Scholar
  5. Zhong, Z., Wen, Z. & Darnell, J. E. Jr Proc. natn. Acad. Sci. U.S.A. 91, 4806–4810 (1994).
    Article ADS CAS Google Scholar
  6. Jacobson, N. G. et al. J. exp. Med. 181, 1755–1762 (1995).
    Article CAS Google Scholar
  7. Bacon, C. M. et al. J. exp. Med. 181, 399–404 (1995).
    Article CAS Google Scholar
  8. Wolf, S. F., Sieburth, D. & Sypek, J. Stem Cells 12, 154–168 (1994).
    Article CAS Google Scholar
  9. Trinchieri, G. A. Rev. Immun. 13, 251–276 (1995).
    Article CAS Google Scholar
  10. Salcedo, T. W., Azzoni, L., Wolf, S. F. & Perussia, B. J. Immun. 151, 2511–2520 (1993).
    CAS PubMed Google Scholar
  11. Paul, W. E. & Seder, R. A. Cell 76, 241–251 (1994).
    Article CAS Google Scholar
  12. Seder, R. A. & Paul, W. E. A. Rev. Immun. 12, 635–673 (1994).
    Article CAS Google Scholar
  13. Shimoda, K. et al. Nature 380, 630–633 (1996).
    Article ADS CAS Google Scholar
  14. Takeda, K. et al. Nature 380, 627–630 (1996).
    Article ADS CAS Google Scholar
  15. Kaplan, M. H., Schindler, U., Smiley, S. T. & Grusby, M. J. Immunity 4, 313–319 (1996).
    Article CAS Google Scholar
  16. Le-Gros, G. et al. J. exp. Med. 172, 921–929 (1990).
    Article CAS Google Scholar
  17. Dybedal, I., Larsen, S. & Jacobsen, S. E. W. J. Immun. 154, 4950–4955 (1995).
    CAS PubMed Google Scholar
  18. van Deursen, J. et al. Cell 74, 621–631 (1993).
    Article CAS Google Scholar
  19. Quelle, F. W. et al. Molec. cell. Biol. 15, 3336–3343 (1995).
    Article CAS Google Scholar
  20. Sarawar, S. R. & Doherty, P. C. J. Virol. 68, 3112–3115 (1994).
    CAS PubMed PubMed Central Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA
    William E. Thierfelder & James N. Ihle
  2. Department of Genetics, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA
    Jan M. van Deursen & Gerard C. Grosveld
  3. Department of Immunology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA
    Ralph A. Tripp, Sally R. Sarawar, Richard T. Carson, Mark Y. Sangster, Dario A. A. Vignali & Peter C. Doherty
  4. Department of Pathology, University of Tennessee Medical School, Memphis, Tennessee, 38163, USA
    Dario A. A. Vignali & Peter C. Doherty
  5. Department of Biochemistry, University of Tennessee Medical School, Memphis, Tennessee, 38163, USA
    James N. Ihle
  6. The First Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113, Japan
    Koh Yamamoto

Authors

  1. William E. Thierfelder
    You can also search for this author inPubMed Google Scholar
  2. Jan M. van Deursen
    You can also search for this author inPubMed Google Scholar
  3. Koh Yamamoto
    You can also search for this author inPubMed Google Scholar
  4. Ralph A. Tripp
    You can also search for this author inPubMed Google Scholar
  5. Sally R. Sarawar
    You can also search for this author inPubMed Google Scholar
  6. Richard T. Carson
    You can also search for this author inPubMed Google Scholar
  7. Mark Y. Sangster
    You can also search for this author inPubMed Google Scholar
  8. Dario A. A. Vignali
    You can also search for this author inPubMed Google Scholar
  9. Peter C. Doherty
    You can also search for this author inPubMed Google Scholar
  10. Gerard C. Grosveld
    You can also search for this author inPubMed Google Scholar
  11. James N. Ihle
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Thierfelder, W., van Deursen, J., Yamamoto, K. et al. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells.Nature 382, 171–174 (1996). https://doi.org/10.1038/382171a0

Download citation

This article is cited by