Skip to main content

Expanding Human T Regulatory Cells with the mTOR-Inhibitor Rapamycin

  • Protocol
  • First Online:
mTOR

Part of the book series: Methods in Molecular Biology ((MIMB,volume 821))

Abstract

CD4+CD25+FOXP3+ T regulatory (Treg) cells are pivotal for the induction and maintenance of peripheral tolerance in both mice and humans. The possibility to use Treg cells for the treatment of T-cell-mediated diseases has recently gained increasing momentum. However, given the limited amount of circulating FOXP3+ Treg cells, efficient methods for their ex vivo expansion are highly desirable. Rapamycin allows for in vitro expansion of murine and human FOXP3+ Treg cells, which maintain their regulatory phenotype and suppressive capacity. Here, we describe in detail the powerful methods for enriching human FOXP3+ Treg cells starting from unfractionated CD4+ T cells or for expanding CD25+-enriched Treg cells in the presence of rapamycin.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
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

Institutional subscriptions

References

  1. Curotto de Lafaille, M. A., and J. J. Lafaille (2009) Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30, 626–635.

    Article  PubMed  CAS  Google Scholar 

  2. Wing, K., and S. Sakaguchi (2010) Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11, 7–13.

    Article  PubMed  CAS  Google Scholar 

  3. Malek, T. R., and I. Castro (2010) Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity. Immunity 33, 153–165.

    Article  PubMed  CAS  Google Scholar 

  4. Roncarolo, M. G., and M. Battaglia (2007) Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat Rev Immunol 7, 585–598.

    Article  PubMed  CAS  Google Scholar 

  5. Battaglia, M., A. Stabilini, and M. G. Roncarolo (2005) Rapamycin selectively expands CD4  +  CD25  +  FoxP3+ regulatory T cells. Blood 105, 4743–4748.

    Article  PubMed  CAS  Google Scholar 

  6. Battaglia, M., A. Stabilini, B. Migliavacca, J. Horejs-Hoeck, T. Kaupper, and M. G. Roncarolo (2006) Rapamycin promotes expansion of functional CD4  +  CD25  +  FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 177, 8338–8347.

    PubMed  CAS  Google Scholar 

  7. Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. Basu S, Golovina T, Mikheeva T, June CH, Riley JL. J Immunol. 2008 May 1;180(9):5794–8.

    PubMed  CAS  Google Scholar 

  8. Stability of human rapamycin-expanded CD4+CD25+ T regulatory cells. Tresoldi E, Dell’albani I, Stabilini A, Jofra T, Valle A, Gagliani N, Bondanza A, Roncarolo MG, Battaglia M. Haematologica. 2011 Sep; 96(9):1357–65.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Italian Telethon Foundation and the Juvenile Diabetes Research Foundation (GJT04014). This study was also supported in part by research funding from BD Biosciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manuela Battaglia .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Battaglia, M., Stabilini, A., Tresoldi, E. (2012). Expanding Human T Regulatory Cells with the mTOR-Inhibitor Rapamycin. In: Weichhart, T. (eds) mTOR. Methods in Molecular Biology, vol 821. Humana Press. https://doi.org/10.1007/978-1-61779-430-8_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-430-8_17

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-429-2

  • Online ISBN: 978-1-61779-430-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics