Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation

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 t...

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Main Authors: Niloufar eSafinia, Cristiano eScotta, Trishan eVaikunthanathan, Robert Ian Lechler, Giovanna eLombardi
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00438/full
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author Niloufar eSafinia
Cristiano eScotta
Trishan eVaikunthanathan
Robert Ian Lechler
Giovanna eLombardi
author_facet Niloufar eSafinia
Cristiano eScotta
Trishan eVaikunthanathan
Robert Ian Lechler
Giovanna eLombardi
author_sort Niloufar eSafinia
collection DOAJ
description 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.
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spelling doaj.art-22055cc817e84e9da0564da6da9205c82022-12-22T00:56:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-08-01610.3389/fimmu.2015.00438159309Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantationNiloufar eSafinia0Cristiano eScotta1Trishan eVaikunthanathan2Robert Ian Lechler3Giovanna eLombardi4King's College LondonKing's College LondonKing's College LondonKing's College LondonKing's College LondonRegulatory 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00438/fullTransplantationtoleranceclinical trialscellular therapyTregs
spellingShingle Niloufar eSafinia
Cristiano eScotta
Trishan eVaikunthanathan
Robert Ian Lechler
Giovanna eLombardi
Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
Frontiers in Immunology
Transplantation
tolerance
clinical trials
cellular therapy
Tregs
title Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
title_full Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
title_fullStr Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
title_full_unstemmed Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
title_short Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation
title_sort regulatory t cells serious contenders in the promise for immunological tolerance in transplantation
topic Transplantation
tolerance
clinical trials
cellular therapy
Tregs
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00438/full
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