Regulatory T-cell therapy in transplantation: moving to the clinic
- PMID: 24186492
- PMCID: PMC3808774
- DOI: 10.1101/cshperspect.a015552
Regulatory T-cell therapy in transplantation: moving to the clinic
Abstract
Regulatory T cells (Tregs) are essential to transplantation tolerance and their therapeutic efficacy is well documented in animal models. Moreover, human Tregs can be identified, isolated, and expanded in short-term ex vivo cultures so that a therapeutic product can be manufactured at relevant doses. Treg therapy is being planned at multiple transplant centers around the world. In this article, we review topics critical to effective implementation of Treg therapy in transplantation. We will address issues such as Treg dose, antigen specificity, and adjunct therapies required for transplant tolerance induction. We will summarize technical advances in Treg manufacturing and provide guidelines for identity and purity assurance of Treg products. Clinical trial designs and Treg manufacturing plans that incorporate the most up-to-date scientific understanding in Treg biology will be essential for harnessing the tolerogenic potential of Treg therapy in transplantation.
References
-
- Allan SE, Crome SQ, Crellin NK, Passerini L, Steiner TS, Bacchetta R, Roncarolo MG, Levings MK 2007. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol 19: 345–354 - PubMed
-
- Baan CC, van der Mast BJ, Klepper M, Mol WM, Peeters AM, Korevaar SS, Balk AH, Weimar W 2005. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation 80: 110–117 - PubMed
-
- Baron U, Floess S, Wieczorek G, Baumann K, Grutzkau A, Dong J, Thiel A, Boeld TJ, Hoffmann P, Edinger M, et al. 2007. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. Eur J Immunol 37: 2378–2389 - PubMed
-
- Battaglia M, Stabilini A, Roncarolo MG 2005. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 105: 4743–4748 - PubMed
-
- Berenson GS, Wattigney WA, Tracy RE, Newman WP 3rd, Srinivasan SR, Webber LS, Dalferes ER Jr, Strong JP 1992. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Am J Cardiol 70: 851–858 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources