Skip to main content

Hedgehog Signalling in T Lymphocyte Development

  • Chapter
  • 527 Accesses

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

T cell development occurs in the thymus, which is seeded by multipotential lymphocyte progenitor cells. These cells then move through a sequence of clearly defined developmental stages at the end of which they become a fully functional mature T cell. For correct organogenesis and T cell development to occur the thymic stroma and the developing thymocytes must interact with one another. Thymocyte development is regulated by factors produced by the thymic stroma. Sonic hedgehog (Shh) is secreted by the thymic stroma and Patched (Ptc), Smoothened (Smo) and the Gli transcription factors are expressed by thymocytes. In the mouse, Shh is involved in the proliferation and efficient progression through the differentiation process, as well as maintaining normal thymic cellularity. In the human, Shh signals to progenitor cells in a paracrine fashion to instruct these cells to maintain the precursor cell pool by increasing their cell viability and inhibiting their expansion and concomitant progression to the next stage in development. Thus, Shh plays an important role in T cell development in both human and mouse.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Manley NR. Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation. Semin Immunol 2000; 12(5):421–428.

    Article  PubMed  CAS  Google Scholar 

  2. Anderson G, Jenkinson EJ. Lymphostromal interactions in thymic development and function. Nat Rev Immunol 2001; 1(1):31–40.

    Article  PubMed  CAS  Google Scholar 

  3. von Boehmer H, Aifantis I, Feinberg J et al. Pleiotropic changes controlled by the preT-cell receptor. Curr Opin Immunol 1999; 11(2):135–142.

    Article  Google Scholar 

  4. Akashi K, Reya T, Dalma-Weiszhausz D et al. Lymphoid precursors. Curr Opin Immunol 2000; 12(2):144–15O.

    Article  PubMed  CAS  Google Scholar 

  5. Shortman K, Vremec D, Corcoran LM et al. The linkage between T-cell and dendritic cell development in the mouse thymus. Immunol Rev 1998; 165:39–46.

    Article  PubMed  CAS  Google Scholar 

  6. Outram SV, Varas A, Pepicelli CV et al. Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte. Immunity 2000; 13(2):187–197.

    Article  PubMed  CAS  Google Scholar 

  7. Li CL, Toda K, Saibara T et al. Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte development. Int Immunopharmacol 2002; 2(6):823–833.

    Article  PubMed  CAS  Google Scholar 

  8. Li CL, Zhang T, Saibara T et al. Thymosin alpha1 accelerates restoration of T cell-mediated neutralizing antibody response in immunocompromised hosts. Int Immunopharmacol 2002; 2(1):39–46.

    Article  PubMed  CAS  Google Scholar 

  9. Ruiz i Altaba A, Sanchez P, Dahmane N. Gli and hedgehog in cancer: Tumours, embryos and stem cells. Nat Rev Cancer 2002; 2(5):361–372.

    Article  PubMed  CAS  Google Scholar 

  10. Mombaerts P, Iacomini J, Johnson RS et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 1992; 68(5):869–877.

    Article  PubMed  CAS  Google Scholar 

  11. Levelt CN, Mombaerts P, Iglesias A et al. Restoration of early thymocyte differentiation in T-cell receptor beta-chain-deficient mutant mice by transmembrane signaling through CD3 epsilon. Proc Natl Acad Sci USA 1993; 90(23):11401–11405.

    Article  PubMed  CAS  Google Scholar 

  12. Chiang C, Litingtung Y, Lee E et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 1996; 383(6599):407–4l3.

    Article  PubMed  CAS  Google Scholar 

  13. Shah DK, Hager-Theodorides AL, Outram SV et al. Reduced thymocyte development in sonic hedgehog knockout embryos. J Immunol 2004; 172(4):2296–2306.

    PubMed  CAS  Google Scholar 

  14. Bhardwaj G, Murdoch B, Wu D et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol 2001; 2(2):172–180.

    Article  PubMed  CAS  Google Scholar 

  15. Charron F, Stein E, Jeong J et al. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 2003; 113(1):11–23.

    Article  PubMed  CAS  Google Scholar 

  16. Pui JC, Allman D, Xu L et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 1999; 11(3):299–308.

    Article  PubMed  CAS  Google Scholar 

  17. Radtke F, Wilson A, Stark G et al. Deficient T cell fate specification in mice with an induced inactivation of Notchl. Immunity 1999; 10(5):547–558.

    Article  PubMed  CAS  Google Scholar 

  18. Izon DJ, Punt JA, Pear WS. Deciphering the role of Notch signaling in lymphopoiesis. Curr Opin Immunol 2002; 14(2):192–199.

    Article  PubMed  CAS  Google Scholar 

  19. Washburn T, Schweighoffer E, Gridley T et al. Notch activity influences the alphabeta versus gammadelta T cell lineage decision. Cell 1997; 88(6):833–843.

    Article  PubMed  CAS  Google Scholar 

  20. Robey E, Chang D, Itano A et al. An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 1996; 87(3):483–492.

    Article  PubMed  CAS  Google Scholar 

  21. Yasutomo K, Doyle C, Miele L et al. The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature 2000; 404(6777):506–510.

    Article  PubMed  CAS  Google Scholar 

  22. Spits H. Development of alphabeta T cells in the human thymus. Nat Rev Immunol 2002; 2(10):760–772.

    Article  PubMed  CAS  Google Scholar 

  23. Sacedon R, Varas A, Hernandez-Lopez C et al. Expression of hedgehog proteins in the human thymus. J Histochem Cytochem 2003; 51(11):1557–1566.

    PubMed  CAS  Google Scholar 

  24. Gutierrez-Frias C, Sacedon R, Hernandez-Lopez C et al. Sonic hedgehog regulates early human thymocyte differentiation by counteracting the IL-7-induced development of CD34+ precursor cells. J Immunol 2004; 173(8):5046–5053.

    PubMed  CAS  Google Scholar 

  25. Okamoto Y, Douek DC, McFarland RD et al. IL-7, the thymus, and naive T cells. Adv Exp Med Biol 2002; 512:81–90.

    PubMed  CAS  Google Scholar 

  26. Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet 1997; 13(1):14–21.

    Article  PubMed  CAS  Google Scholar 

  27. Hager-Theodorides AL, Outram SV, Shah DK et al. Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol 2002; 169(10):5496–5504.

    PubMed  CAS  Google Scholar 

  28. Tsai PT, Lee RA, Wu H. BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Blood 2003; 102(12):3947–3953.

    Article  PubMed  CAS  Google Scholar 

  29. Mulroy T, McMahon JA, Burakoff SJ et al. Wnt-1 and Wnt-4 regulate thymic cellularity. Eur J Immunol 2002; 32(4):967–971.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Outram, S., Hager-Theodorides, A.L., Crompton, T. (2006). Hedgehog Signalling in T Lymphocyte Development. In: Shh and Gli Signalling and Development. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39957-7_10

Download citation

Publish with us

Policies and ethics