2015
DOI: 10.3389/fimmu.2015.00438
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Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation

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 translatio… Show more

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Cited by 108 publications
(102 citation statements)
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References 169 publications
(186 reference statements)
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“…Unlike drug-based immunosuppressive regimens which have detrimental effects on the patient's wellbeing [25] and do not offer a complete treatment option [14,23], Treg therapy has the potential to be a highly personalized technique which allows for the manipulation of a patient's immune system in order to promote immunological tolerance. The essence of what Treg therapy entails can be split into three key steps: cell isolation, ex vivo expansion and subsequent re-infusion of Tregs ( Figure 1A).…”
Section: Regulatory T-cell Therapy -Current Applicationsmentioning
confidence: 99%
See 1 more Smart Citation
“…Unlike drug-based immunosuppressive regimens which have detrimental effects on the patient's wellbeing [25] and do not offer a complete treatment option [14,23], Treg therapy has the potential to be a highly personalized technique which allows for the manipulation of a patient's immune system in order to promote immunological tolerance. The essence of what Treg therapy entails can be split into three key steps: cell isolation, ex vivo expansion and subsequent re-infusion of Tregs ( Figure 1A).…”
Section: Regulatory T-cell Therapy -Current Applicationsmentioning
confidence: 99%
“…Although not as well characterized as tTregs, pTregs have been implicated with the induction and maintenance of tolerance in vivo, mostly through the secretion of immunosuppressive cytokines. It is believed that at least two types of pTregs exist, namely Type-I regulatory T-cells (Tr1) and T helper 3 cells (Th3) which secrete high levels of IL-10 and transforming growth factor (TGF)-β, respectively [23]. A feature of particular interest is the fact that pTregs may be generated from naïve T-cells in vitro, a phenomenon which has been applied to generate Tr1 cells for clinical application in Crohn's disease [24] (detailed below).…”
mentioning
confidence: 99%
“…35 The general consensus throughout these studies concluded that donor antigen-specific regulatory T cells are more effective compared with polyclonal regulatory T cells. 36 In a pilot study, 37 tolerance was induced by using a novel regulatory T-cell-based cell therapy in livingdonor liver transplant. Adoptive transfer of an ex vivo-generated regulatory T-cell-enriched cell product was conducted in 10 consecutive adult patients early after liver transplant.…”
Section: Tolerogenic Dendritic Cellsmentioning
confidence: 99%
“…The most reported protocols include anti-CD3/anti-CD28-coated beads for T cell stimulation, along with administration of human IL-2 and the immunosuppressor drug Rapamycin [2,3], which favors Tregs growth instead of the proliferation of effector CD4+ T. To date, several clinical studies have been performed, and the data indicates that the administration of huTregs is safe even in high doses [4] and seems to ameliorate the symptoms of Graft versus Host Disease (GvHD) in some cases; however, this has not been accomplished in all patients, thus demonstrating the need for more knowledge and treatment alternatives [5][6][7][8]. One of the limitations of huTregs effectiveness is the potential lost of their functional stability (or plasticity); in other words, huTregs may convert from a suppressive to an inflammatory phenotype [9]. Among the molecules that could be considered to optimize the production of huTregs, we sought to study IL-33 based on its recent role in the generation of tolerance [10,11].…”
Section: Introductionmentioning
confidence: 99%