Abstract
Regulatory T lymphocytes expressing CD4, high levels of CD25, and the transcription factor Foxp3 play a crucial role in the control of immune responses to self and nonself antigens. In contrast to immunosuppressive drugs currently used to treat immunopathology, these cells act in a very specific manner. Consequently, their clinical potential in the treatment of autoimmune disorders, inflammatory diseases, graft-versus-host disease, and allograft rejection is currently extensively studied in experimental animal models as well as in clinical trials. We have previously shown that appropriately in vitro stimulated CD4+CD25high regulatory T cells can be used to prevent rejection of bone marrow, skin, and heart allografts in the Mouse. We here describe the protocols used in our laboratory to isolate mouse regulatory T cells, to stimulate them in vitro in order to enrich in cells specific for donor-antigens, and to transplant bone marrow under cover of regulatory T cells. Thus, generated hematopoietic chimeras may subsequently be transplanted with solid tissues and organs from the same donor.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. (2008) Regulatory T cells and immune tolerance, Cell 133, 775–787.
Tang, Q., and Bluestone, J. A. (2008) The Foxp3+ regulatory T cell: a jack of all trades, master of regulation, Nat. Immunol. 9, 239–244.
Ziegler, S. F. (2006) FOXP3: of mice and men, Annu. Rev. Immunol. 24, 209–226.
Beyer, M., and Schultze, J. L. (2006) Regulatory T cells in cancer, Blood 108, 804–811.
Belkaid, Y., Blank, R. B., and Suffia, I. (2006) Natural regulatory T cells and parasites: a common quest for host homeostasis, Immunol. Rev. 212, 287–300.
Aluvihare, V. R., Kallikourdis, M., and Betz, A. G. (2004) Regulatory T cells mediate maternal tolerance to the fetus, Nat. Immunol. 5, 266–271.
Joffre, O., Gorsse, N., Romagnoli, P., Hudrisier, D., and van Meerwijk, J. P. M. (2004) Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes, Blood 103, 4216–4221.
Joffre, O., and van Meerwijk, J. P. M. (2006) CD4+CD25+ regulatory T lymphocytes in bone marrow transplantation, Sem. Immunol. 18, 128–135.
Itoh, M., Takahashi, T., Sakaguchi, N., Kuniyasu, Y., Shimizu, J., Otsuka, F., and Sakaguchi, S. (1999) Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance, J. Immunol. 162, 5317–5326.
Joffre, O., Santolaria, T., Calise, D., Al Saati, T., Hudrisier, D., Romagnoli, P., and van Meerwijk, J. P. M. (2008) Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes, Nat. Med. 14, 88–92.
Coudert, J. D., Coureau, C., and Guery, J. C. (2002) Preventing NK cell activation by donor dendritic cells enhances allospecific CD4 T cell priming and promotes Th type 2 responses to transplantation antigens, J. Immunol. 169, 2979–2987.
Corry, R. J., Winn, H. J., and Russell, P. S. (1973) Primarily vascularized allografts of hearts in mice. The role of H-2D, H-2K, and non-H-2 antigens in rejection, Transplantation 16, 343–350.
Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G., Hamann, A., Wagner, H., Huehn, J., and Sparwasser, T. (2007) Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease, J. Exp. Med. 204, 57–63.
Wang, Y., Kissenpfennig, A., Mingueneau, M., Richelme, S., Perrin, P., Chevrier, S., Genton, C., Lucas, B., DiSanto, J. P., Acha-Orbea, H., Malissen, B., and Malissen, M. (2008) Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells, J. Immunol. 180, 1565–1575.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Nouzé, C., Pasquet, L., van Meerwijk, J.P.M. (2011). In Vitro Expansion of Alloantigen-Specific Regulatory T Cells and Their Use in Prevention of Allograft Rejection. In: Kassiotis, G., Liston, A. (eds) Regulatory T Cells. Methods in Molecular Biology, vol 707. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-979-6_12
Download citation
DOI: https://doi.org/10.1007/978-1-61737-979-6_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-978-9
Online ISBN: 978-1-61737-979-6
eBook Packages: Springer Protocols