Skip to main content
SpringerLink
Log in

Studying Peripheral T Cell Homeostasis in Mice: A Concise Technical Review

  • Protocol
  • First Online:
T-Cell Receptor Signaling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2111))

Abstract

For several years, it was believed that the thymus was entirely responsible for maintaining T cell homeostasis. Today, it is well-known that homeostatic peripheral mechanisms are essential in order to maintain T cell numbers and diversity constant in the periphery. Naïve and memory T cells require continual access to self-peptide MHC class I and II molecules and/or cytokines to survive in the periphery. Under normal conditions, homeostatic resources are low, and lymphocytes undergo very slow proliferation and survive. Following T cell depletion, the bioavailability of homeostatic resources is significantly increased, and T cell proliferation is dramatically augmented. The development of lymphopenic mouse models has helped our current understanding of factors involved in the regulation of peripheral T cell homeostasis. In this minireview, we will give a brief overview about basic techniques used to study peripheral T cell homeostasis in mice.

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 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE (1996) Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol 156(12):4609–4616

    CAS  PubMed  Google Scholar 

  2. Berzins SP, Godfrey DI, Miller JF, Boyd RL (1999) A central role for thymic emigrants in peripheral T cell homeostasis. Proc Natl Acad Sci U S A 96(17):9787–9791

    Article  CAS  Google Scholar 

  3. Miller JFAP (1962) Immunological significance of the thymus of the adult mouse. Nature 195(4848):1318–1319. https://doi.org/10.1038/1951318a0

    Article  Google Scholar 

  4. Gauthier SD, Leboeuf D, Manuguerra-Gagne R, Gaboury L, Guimond M (2015) Stromal-derived factor-1alpha and interleukin-7 treatment improves homeostatic proliferation of naive CD4(+) T cells after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 21(10):1721–1731. https://doi.org/10.1016/j.bbmt.2015.06.019

    Article  CAS  PubMed  Google Scholar 

  5. Gauthier SD, Moutuou MM, Daudelin F, Leboeuf D, Guimond M (2018) IL-7 is the limiting homeostatic factor that constrains homeostatic proliferation of CD8(+) T cells after allogeneic stem cell transplantation and graft-versus-host disease. Biol Blood Marrow Transplant. https://doi.org/10.1016/j.bbmt.2018.12.066

    Article  CAS  Google Scholar 

  6. Murali-Krishna K, Lau LL, Sambhara S, Lemonnier F, Altman J, Ahmed R (1999) Persistence of memory CD8 T cells in MHC class I-deficient mice. Science (New York, NY) 286(5443):1377. https://doi.org/10.1126/science.286.5443.1377

    Article  CAS  Google Scholar 

  7. Sandau MM, Winstead CJ, Jameson SC (2007) IL-15 is required for sustained lymphopenia-driven proliferation and accumulation of CD8 T cells. J Immunol 179(1):120–125

    Article  CAS  Google Scholar 

  8. Lenz DC, Kurz SK, Lemmens E, Schoenberger SP, Sprent J, Oldstone MB, Homann D (2004) IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc Natl Acad Sci U S A 101(25):9357–9362. https://doi.org/10.1073/pnas.0400640101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Purton JF, Tan JT, Rubinstein MP, Kim DM, Sprent J, Surh CD (2007) Antiviral CD4+ memory T cells are IL-15 dependent. J Exp Med 204(4):951–961. https://doi.org/10.1084/jem.20061805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fry TJ, Connick E, Falloon J, Lederman MM, Liewehr DJ, Spritzler J, Steinberg SM, Wood LV, Yarchoan R, Zuckerman J, Landay A, Mackall CL (2001) A potential role for interleukin-7 in T-cell homeostasis. Blood 97(10):2983–2990

    Article  CAS  Google Scholar 

  11. Guimond M, Veenstra RG, Grindler DJ, Zhang H, Cui Y, Murphy RD, Kim SY, Na R, Hennighausen L, Kurtulus S, Erman B, Matzinger P, Merchant MS, Mackall CL (2009) Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nat Immunol 10(2):149–157. https://doi.org/10.1038/ni.1695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD (2001) IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98(15):8732–8737. https://doi.org/10.1073/pnas.161126098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goldrath AW, Bogatzki LY, Bevan MJ (2000) Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J Exp Med 192(4):557–564

    Article  CAS  Google Scholar 

  14. Abdelsamed HA, Zebley CC, Youngblood B (2017) In vitro homeostatic proliferation of human CD8 T cells. Bio Protoc 7(22). https://doi.org/10.21769/BioProtoc.2619

  15. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 181(4):1519–1526

    Article  Google Scholar 

  16. Rocha B, Penit C, Baron C, Vasseur F, Dautigny N, Freitas AA (1990) Accumulation of bromodeoxyuridine-labeled cells in central and peripheral lymphoid organs: minimal estimates of production and turnover rates of mature lymphocytes. Eur J Immunol 20(8):1697–1708. https://doi.org/10.1002/eji.1830200812

    Article  CAS  PubMed  Google Scholar 

  17. Tough DF, Sprent J (1994) Turnover of naive- and memory-phenotype T cells. J Exp Med 179(4):1127–1135

    Article  CAS  Google Scholar 

  18. Parretta E, Cassese G, Santoni A, Guardiola J, Vecchio A, Di Rosa F (2008) Kinetics of in vivo proliferation and death of memory and naive CD8 T cells: parameter estimation based on 5-bromo-2′-deoxyuridine incorporation in spleen, lymph nodes, and bone marrow. J Immunol 180(11):7230–7239

    Article  CAS  Google Scholar 

  19. Dulude G, Roy DC, Perreault C (1999) The effect of graft-versus-host disease on T cell production and homeostasis. J Exp Med 189(8):1329–1342

    Article  CAS  Google Scholar 

  20. Lyons AB, Parish CR (1994) Determination of lymphocyte division by flow cytometry. J Immunol Methods 171(1):131–137

    Article  CAS  Google Scholar 

  21. Quah BJ, Parish CR (2012) New and improved methods for measuring lymphocyte proliferation in vitro and in vivo using CFSE-like fluorescent dyes. J Immunol Methods 379(1–2):1–14. https://doi.org/10.1016/j.jim.2012.02.012

    Article  CAS  PubMed  Google Scholar 

  22. Powrie F (1995) T cells in inflammatory bowel disease: protective and pathogenic roles. Immunity 3(2):171–174

    Article  CAS  Google Scholar 

  23. Budd RC, Cerottini JC, Horvath C, Bron C, Pedrazzini T, Howe RC, MacDonald HR (1987) Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. J Immunol 138(10):3120

    CAS  PubMed  Google Scholar 

  24. Desbarats J, Wade T, Wade WF, Newell MK (1999) Dichotomy between naïve and memory CD4(+) T cell responses to Fas engagement. Proc Natl Acad Sci U S A 96(14):8104–8109

    Article  CAS  Google Scholar 

  25. Moses CT, Thorstenson KM, Jameson SC, Khoruts A (2003) Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells. Proc Natl Acad Sci U S A 100(3):1185. https://doi.org/10.1073/pnas.0334572100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ge Q, Bai A, Jones B, Eisen HN, Chen J (2004) Competition for self-peptide-MHC complexes and cytokines between naïve and memory CD8+ T cells expressing the same or different T cell receptors. Proc Natl Acad Sci U S A 101(9):3041. https://doi.org/10.1073/pnas.0307339101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Troy AE, Shen H (2003) Cutting edge: homeostatic proliferation of peripheral T lymphocytes is regulated by clonal competition. J Immunol 170(2):672–676

    Article  CAS  Google Scholar 

  28. Min B, Yamane H, Hu-Li J, Paul WE (2005) Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms. J Immunol 174(10):6039–6044

    Article  CAS  Google Scholar 

  29. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM et al (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68(5):855–867

    Article  CAS  Google Scholar 

  30. Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75(2):274–282

    Article  CAS  Google Scholar 

  31. Schluns KS, Kieper WC, Jameson SC, Lefrancois L (2000) Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol 1(5):426–432. https://doi.org/10.1038/80868

    Article  CAS  PubMed  Google Scholar 

  32. Vivien L, Benoist C, Mathis D (2001) T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. Int Immunol 13(6):763–768

    Article  CAS  Google Scholar 

  33. Ramsey C, Rubinstein MP, Kim DM, Cho JH, Sprent J, Surh CD (2008) The lymphopenic environment of CD132 (common gamma-chain)-deficient hosts elicits rapid homeostatic proliferation of naive T cells via IL-15. J Immunol 180(8):5320–5326

    Article  CAS  Google Scholar 

  34. Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S, Peschon JJ (2000) Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191(5):771–780

    Article  CAS  Google Scholar 

  35. Ge Q, Rao VP, Cho BK, Eisen HN, Chen J (2001) Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/MHC epitopes and strength of their interaction with T cell receptors. Proc Natl Acad Sci U S A 98(4):1728–1733. https://doi.org/10.1073/pnas.98.4.1728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Le Campion A, Bourgeois C, Lambolez F, Martin B, Leaument S, Dautigny N, Tanchot C, Penit C, Lucas B (2002) Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes. Proc Natl Acad Sci U S A 99(7):4538–4543. https://doi.org/10.1073/pnas.062621699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. James E, Chai JG, Dewchand H, Macchiarulo E, Dazzi F, Simpson E (2003) Multiparity induces priming to male-specific minor histocompatibility antigen, HY, in mice and humans. Blood 102(1):388–393. https://doi.org/10.1182/blood-2002-10-3170

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Cancer Research Society of Canada (grant no. 22669 and 24380 to M.G.) and in part by a grant from the Foundation de l’Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.

Author information

Authors and Affiliations

  1. Division Immunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada

    Martin Guimond

  2. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada

    Moutuaata M. Moutuou, Simon-David Gauthier & Martin Guimond

  3. Département de Biochimie et médecine moléculaire, Université de Montréal, Montréal, QC, Canada

    Nicolas Chen

  4. Skolkovo Institute of Science and Technology, Moscow, Russia

    Dominique Leboeuf

Authors
  1. Moutuaata M. Moutuou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon-David Gauthier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicolas Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dominique Leboeuf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Guimond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Guimond .

Editor information

Editors and Affiliations

  1. Department of Pathogen Biology, Huazhong University of Science and Technology, Wuhan, China

    Chaohong Liu

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Moutuou, M.M., Gauthier, SD., Chen, N., Leboeuf, D., Guimond, M. (2020). Studying Peripheral T Cell Homeostasis in Mice: A Concise Technical Review. In: Liu, C. (eds) T-Cell Receptor Signaling. Methods in Molecular Biology, vol 2111. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0266-9_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0266-9_21

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0265-2

  • Online ISBN: 978-1-0716-0266-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation