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Safinia N, Scotta C, Vaikunthanathan T, et al. Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation. Front Immunol. 2015;6:438doi: 10.3389/fimmu.2015.00438.
Safinia, N., Scotta, C., Vaikunthanathan, T., Lechler, R. I., & Lombardi, G. (2015). Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation. Frontiers in immunology, 6438. https://doi.org/10.3389/fimmu.2015.00438
Safinia, Niloufar, et al. "Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation." Frontiers in immunology vol. 6 (2015): 438. doi: https://doi.org/10.3389/fimmu.2015.00438
Safinia N, Scotta C, Vaikunthanathan T, Lechler RI, Lombardi G. Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation. Front Immunol. 2015 Aug 31;6:438. doi: 10.3389/fimmu.2015.00438. eCollection 2015. PMID: 26379673; PMCID: PMC4553385.
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Front Immunol. 2015 Aug 31;6:438. doi: 10.3389/fimmu.2015.00438. eCollection 2015.

Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation.

Frontiers in immunology

Niloufar Safinia, Cristiano Scotta, Trishan Vaikunthanathan, Robert I Lechler, Giovanna Lombardi

Affiliations

  1. MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King's College London , London , UK.

PMID: 26379673 PMCID: PMC4553385 DOI: 10.3389/fimmu.2015.00438

Abstract

Regulatory T cells (Tregs) play an important role in immunoregulation and have been shown in animal models to promote transplantation tolerance and curb autoimmunity following their adoptive transfer. The safety and potential therapeutic efficacy of these cells has already been reported in Phase I trials of bone-marrow transplantation and type I diabetes, the success of which has motivated the broadened application of these cells in solid-organ transplantation. Despite major advances in the clinical translation of these cells, there are still key questions to be addressed to ensure that Tregs attest their reputation as ideal candidates for tolerance induction. In this review, we will discuss the unique traits of Tregs that have attracted such fame in the arena of tolerance induction. We will outline the protocols used for their ex vivo expansion and discuss the future directions of Treg cell therapy. In this regard, we will review the concept of Treg heterogeneity, the desire to isolate and expand a functionally superior Treg population and report on the effect of differing culture conditions. The relevance of Treg migratory capacity will also be discussed together with methods of in vivo visualization of the infused cells. Moreover, we will highlight key advances in the identification and expansion of antigen-specific Tregs and discuss their significance for cell therapy application. We will also summarize the clinical parameters that are of importance, alongside cell manufacture, from the choice of immunosuppression regimens to the number of injections in order to direct the success of future efficacy trials of Treg cell therapy. Years of research in the field of tolerance have seen an accumulation of knowledge and expertise in the field of Treg biology. This perpetual progression has been the driving force behind the many successes to date and has put us now within touching distance of our ultimate success, immunological tolerance.

Keywords: cellular therapy; clinical trials; tolerance; transplantation; tregs

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