Skip to main content
SpringerLink
Log in

Development of γδ T Cells, the Special-Force Soldiers of the Immune System

  • Protocol
T-Cell Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1323))

Abstract

While the functions of αβ T cells in host resistance to pathogen infection are understood in far more detail than those of γδ lineage T cells, γδ T cells perform critical, essential functions during immune responses that cannot be compensated by αβ T cells. Accordingly, it is essential to understand how the development of γδ T cells is controlled so that their generation and function might be manipulated in future for therapeutic benefit. This introductory chapter will cover the basic processes that underlie γδ T cell development in the thymus, as well as the current understanding of how they are controlled.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Institutional subscriptions

References

  1. Hayday AC (2000) [gamma][delta] cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026

    Article  CAS  PubMed  Google Scholar 

  2. Carding SR, Egan PJ (2002) Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2:336–345

    Article  CAS  PubMed  Google Scholar 

  3. Vantourout P, Hayday A (2013) Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol 13:88–100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sheridan BS, Romagnoli PA, Pham QM et al (2013) gammadelta T cells exhibit multifunctional and protective memory in intestinal tissues. Immunity 39:184–195

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. King DP, Hyde DM, Jackson KA et al (1999) Cutting edge: protective response to pulmonary injury requires gamma delta T lymphocytes. J Immunol 162:5033–5036

    CAS  PubMed  Google Scholar 

  6. Ramsburg E, Tigelaar R, Craft J et al (2003) Age-dependent requirement for gammadelta T cells in the primary but not secondary protective immune response against an intestinal parasite. J Exp Med 198:1403–1414

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Girardi M, Oppenheim DE, Steele CR et al (2001) Regulation of cutaneous malignancy by {gamma}{delta} T cells. Science 20:20

    Google Scholar 

  8. Chen Y, Chou K, Fuchs E et al (2002) Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 99:14338–14343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Sharp LL, Jameson JM, Cauvi G et al (2005) Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1. Nat Immunol 6:73–79

    Article  CAS  PubMed  Google Scholar 

  10. Nedellec S, Bonneville M, Scotet E (2010) Human Vgamma9Vdelta2 T cells: from signals to functions. Semin Immunol 22:199–206

    Article  CAS  PubMed  Google Scholar 

  11. Meraviglia S, Eberl M, Vermijlen D et al (2010) In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients. Clin Exp Immunol 161:290–297

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Cai Y, Fleming C, Yan J (2012) New insights of T cells in the pathogenesis of psoriasis. Cell Mol Immunol 9:302–309

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Wu P, Wu D, Ni C et al (2014) gammadeltaT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 40:785–800

    Article  CAS  PubMed  Google Scholar 

  14. Born WK, Kemal Aydintug M, O’Brien RL (2013) Diversity of gammadelta T-cell antigens. Cell Mol Immunol 10:13–20

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Rock EP, Sibbald PR, Davis MM et al (1994) CDR3 length in antigen-specific immune receptors. J Exp Med 179:323–328

    Article  CAS  PubMed  Google Scholar 

  16. Lauritsen JP, Haks MC, Lefebvre JM et al (2006) Recent insights into the signals that control alphabeta/gammadelta-lineage fate. Immunol Rev 209:176–190

    Article  PubMed  Google Scholar 

  17. Xiong N, Raulet DH (2007) Development and selection of gammadelta T cells. Immunol Rev 215:15–31

    Article  CAS  PubMed  Google Scholar 

  18. Bonneville M, O’Brien RL, Born WK (2010) Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 10:467–478

    Article  CAS  PubMed  Google Scholar 

  19. O’Brien RL, Born WK (2010) gammadelta T cell subsets: a link between TCR and function? Semin Immunol 22:193–198

    Article  PubMed Central  PubMed  Google Scholar 

  20. Jin Y, Xia M, Saylor CM et al (2010) Cutting edge: intrinsic programming of thymic gammadeltaT cells for specific peripheral tissue localization. J Immunol 185:7156–7160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Lee SY, Stadanlick J, Kappes DJ et al (2010) Towards a molecular understanding of the differential signals regulating alphabeta/gammadelta T lineage choice. Semin Immunol 22:237–246

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Lewis JM, Girardi M, Roberts SJ et al (2006) Selection of the cutaneous intraepithelial gammadelta + T cell repertoire by a thymic stromal determinant. Nat Immunol 7:843–850

    Article  CAS  PubMed  Google Scholar 

  23. Pereira P, Zijlstra M, McMaster J et al (1992) Blockade of transgenic gamma delta T cell development in beta 2-microglobulin deficient mice. EMBO J 11:25–31

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Coffey F, Lee SY, Buus TB et al (2014) The TCR ligand-inducible expression of CD73 marks gammadelta lineage commitment and a metastable intermediate in effector specification. J Exp Med 211:329–343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Ribot JC, deBarros A, Pang DJ et al (2009) CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets. Nat Immunol 10:427–436

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kreslavsky T, Garbe AI, Krueger A et al (2008) T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis. J Exp Med 205:1173–1186

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Pennington DJ, Silva-Santos B, Shires J et al (2003) The inter-relatedness and interdependence of mouse T cell receptor gammadelta+ and alphabeta+ cells. Nat Immunol 4:991–998

    Article  CAS  PubMed  Google Scholar 

  28. Melichar HJ, Narayan K, Der SD et al (2007) Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13. Science 315:230–233

    Article  CAS  PubMed  Google Scholar 

  29. Roberts NA, White AJ, Jenkinson WE et al (2012) Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium. Immunity 36:427–437

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Silva-Santos B, Pennington DJ, Hayday AC (2005) Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors. Science 307:925–928

    Article  CAS  PubMed  Google Scholar 

  31. Petrie HT, Scollay R, Shortman K (1992) Commitment to the T cell receptor-alpha beta or -gamma delta lineages can occur just prior to the onset of CD4 and CD8 expression among immature thymocytes. Eur J Immunol 22:2185–2188

    Article  CAS  PubMed  Google Scholar 

  32. Ciofani M, Knowles GC, Wiest DL et al (2006) Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation. Immunity 25:105–116

    Article  CAS  PubMed  Google Scholar 

  33. Narayan K, Kang J (2010) Disorderly conduct in gammadelta versus alphabeta T cell lineage commitment. Semin Immunol 22:222–227

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Wong GW, Zuniga-Pflucker JC (2010) gammadelta and alphabeta T cell lineage choice: resolution by a stronger sense of being. Semin Immunol 22:228–236

    Article  CAS  PubMed  Google Scholar 

  35. Hayes SM, Love PE (2006) Strength of signal: a fundamental mechanism for cell fate specification. Immunol Rev 209:170–175

    Article  PubMed  Google Scholar 

  36. Hayes SM, Li L, Love PE (2005) TCR signal strength influences alphabeta/gammadelta lineage fate. Immunity 22:583–593

    Article  CAS  PubMed  Google Scholar 

  37. Haks MC, Lefebvre JM, Lauritsen JP et al (2005) Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity 22:595–606

    Article  CAS  PubMed  Google Scholar 

  38. Kreslavsky T, von Boehmer H (2010) gammadeltaTCR ligands and lineage commitment. Semin Immunol 22:214–221

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Meyer C, Zeng X, Chien YH (2010) Ligand recognition during thymic development and gammadelta T cell function specification. Semin Immunol 22:207–213

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Havran WL, Allison JP (1988) Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 335: 443–445

    Article  CAS  PubMed  Google Scholar 

  41. Boyden LM, Lewis JM, Barbee SD et al (2008) Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gammadelta T cells. Nat Genet 40:656–662

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Lauritsen JP, Wong GW, Lee SY et al (2009) Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity 31:565–575

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Prinz I, Silva-Santos B, Pennington DJ (2013) Functional development of gammadelta T cells. Eur J Immunol 43:1988–1994

    Article  CAS  PubMed  Google Scholar 

  44. Turchinovich G, Hayday AC (2011) Skint-1 identifies a common molecular mechanism for the development of interferon-gamma-secreting versus interleukin-17-secreting gammadelta T cells. Immunity 35:59–68

    Article  CAS  PubMed  Google Scholar 

  45. Narayan K, Sylvia KE, Malhotra N et al (2012) Intrathymic programming of effector fates in three molecularly distinct gammadelta T cell subtypes. Nat Immunol 13:511–518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Jensen KD, Su X, Shin S et al (2008) Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity 29:90–100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Wencker M, Turchinovich G, Di Marco BR et al (2014) Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness. Nat Immunol 15:80–87

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blood Cell Development and Function Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA

    David L. Wiest

Authors
  1. David L. Wiest
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David L. Wiest .

Editor information

Editors and Affiliations

  1. Laboratory of Immune Cell Biology, National Institutes of Health National Cancer Institute, Bethesda, Maryland, USA

    Rémy Bosselut

  2. Laboratory of Immune Cell Biology, National Institutes of Health National Cancer Institute, Bethesda, Maryland, USA

    Melanie S. Vacchio

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Wiest, D.L. (2016). Development of γδ T Cells, the Special-Force Soldiers of the Immune System. In: Bosselut, R., S. Vacchio, M. (eds) T-Cell Development. Methods in Molecular Biology, vol 1323. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2809-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2809-5_2

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2808-8

  • Online ISBN: 978-1-4939-2809-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation