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Trawling for treasure: tales of T-bet

Nature Immunology volume 8, pages 448–450 (2007)Cite this article

Discovering the transcription factors that direct lineage commitment in the T helper cell was a formidable task. Laurie Glimcher describes how she and Susanne Szabo hunted down T-bet, a transcription factor that is a 'master regulator' of commitment to the T helper type 1 lineage.

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References

  1. Cantor, H. & Boyse, E.A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J. Exp. Med. 141, 1376–1389 (1975).

    Article  CAS  Google Scholar 

  2. Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A. & Coffman, R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986).

    CAS  PubMed  Google Scholar 

  3. Liou, H-C., Boothby, M.R. & Glimcher, L.H. Distinct cloned class II MHC DNA-binding proteins recognize the X box transcription element. Science 242, 69–71 (1988).

    Article  CAS  Google Scholar 

  4. Liou, H.C. et al. A new member of the leucine zipper class of proteins that binds to the HLA DRα promoter. Science 247, 1581–1584 (1990).

    Article  CAS  Google Scholar 

  5. Boothby, M., Gravallese, E., Liou, H-C. & Glimcher, L.H.A. DNA binding protein regulated by IL-4 and by differentiation in B cells. Science 242, 1559–1562 (1988).

    Article  CAS  Google Scholar 

  6. Crabtree, G. Contingent genetic regulatory events in T lymphocyte activation. Science 243, 355–361 (1989).

    Article  CAS  Google Scholar 

  7. Rooney, J.W., Hoey, T. & Glimcher, L.H. Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2, 473–483 (1995).

    Article  CAS  Google Scholar 

  8. Ho, I-C., Hodge, M.R., Rooney, J.W. & Glimcher, L.H. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973–983 (1996).

    Article  CAS  Google Scholar 

  9. Ho, I-C., Lo, D. & Glimcher, L.H. C-maf promotes Th2 and attenuates Th1 differentiation by both IL-4 dependent and independent mechanisms. J. Exp. Med. 188, 1859–1866 (1998).

    Article  CAS  Google Scholar 

  10. Kim, J., Ho, I.C., Grusby, M. & Glimcher, L.H. The transcription factor c-Maf controls the production of IL-4 but not other Th2 cytokines. Immunity 10, 745–751 (1999b).

    Article  CAS  Google Scholar 

  11. Zheng, W. & Flavell, R.A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89, 587–596 (1997).

    Article  CAS  Google Scholar 

  12. Zhang, D.H., Cohn, L., Ray, P., Bottomly, K. & Ray, A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272, 21597–21603 (1997).

    Article  CAS  Google Scholar 

  13. Szabo, S.J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655–669 (2000).

    Article  CAS  Google Scholar 

  14. Szabo, S.J. et al. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295, 338–342 (2002).

    Article  CAS  Google Scholar 

  15. Hwang, E.S., Szabo, S.J., Schwartzberg, P.L. & Glimcher, L.H. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307, 430–433 (2005).

    Article  CAS  Google Scholar 

  16. Hwang, E.S., Hong, J.H. & Glimcher, L.H. IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508. J. Exp. Med. 202, 1289–1300 (2005).

    Article  CAS  Google Scholar 

  17. Szabo, S.J., Sullivan, B.M., Peng, S.L. & Glimcher, L.H. Molecular mechanisms regulating Th1 immune responses. Annu. Rev. Immunol. 21, 713–758 (2003).

    Article  CAS  Google Scholar 

  18. Lugo-Villarino, G., Ito, S.C., Klinman, D.M. & Glimcher, L.H. The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells. Proc. Natl. Acad. Sci. USA 102, 13248–13253 (2005).

    Article  CAS  Google Scholar 

  19. Sullivan, B.M. et al. Increased susceptibility of mice lacking T-bet to infection with Mycobacterium tuberculosis correlates with increased IL-10 and decreased IFN-γ production. J. Immunol. 175, 4593–4602 (2005).

    Article  CAS  Google Scholar 

  20. Peng, S.L., Townsend, M.J., Hecht, J.L., White, I.A. & Glimcher, L.H. T-bet regulates metastasis rate in a murine model of primary prostate cancer. Cancer Res. 64, 452–455 (2004).

    Article  CAS  Google Scholar 

  21. Peng, S.L., Szabo, S.J. & Glimcher, L.H. T-bet regulates IgG class switching and pathogenic autoantibody production. Proc. Natl. Acad. Sci. USA 99, 5545–5550 (2002).

    Article  CAS  Google Scholar 

  22. Bettelli, E. et al. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J. Exp. Med. 200, 79–87 (2004).

    Article  CAS  Google Scholar 

  23. Juedes, A., Rodrigo, E., Togher, L., Glimcher, L.H. & von Herrath, M. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. J. Exp. Med. 199, 1153–1162 (2004).

    Article  CAS  Google Scholar 

  24. Wang, J. et al. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J. Clin. Invest. 116, 414–421 (2006).

    Article  CAS  Google Scholar 

  25. Finotto, S. et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338 (2002).

    Article  CAS  Google Scholar 

  26. Tantisira, K.G. et al. TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc. Natl. Acad. Sci. USA 101, 18099–18104 (2004).

    Article  CAS  Google Scholar 

  27. Sullivan, B.M., Juedes, A., Szabo, S.J., von Herrath, M. & Glimcher, L.H. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc. Natl. Acad. Sci. USA 100, 15818–15823 (2003).

    Article  CAS  Google Scholar 

  28. Townsend, M.J. et al. T-bet regulates the terminal maturation and homeostasis of NK and Vα14i NKT cells. Immunity 20, 477–494 (2004).

    Article  CAS  Google Scholar 

  29. Lugo-Villarino, G., Maldonado-Lopez, R., Possemato, R., Penaranda, C. & Glimcher, L.H. T-bet is required for optimal production of IFN-γ and antigen-specific T cell activation by dendritic cells. Proc. Natl. Acad. Sci. USA 100, 7749–7754 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

I thank the graduate students and postdoctoral fellows I have worked with over the past two decades and the US National Institutes of Health for its continued support since 1982.

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Authors and Affiliations

  1. Laurie H. Glimcher is in the Department of Immunology and Infectious Diseases, and the Department of Medicine, Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts 02115, USA. lglimche@hsph.harvard.edu,

    Laurie H Glimcher

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Glimcher, L. Trawling for treasure: tales of T-bet. Nat Immunol 8, 448–450 (2007). https://doi.org/10.1038/ni0507-448

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