Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells

Zwang, Nicholas A.; Leventhal, Joseph R.

doi:10.1681/asn.2016111206

Cited by 30 publications

(31 citation statements)

References 190 publications

(197 reference statements)

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“…Regulatory T cells are broadly classified as thymus derived (natural) Tregs, or peripheral inducible Tregs. Inducible Tregs can be generated from natural Tregs or naïve CD4 1 CD25 2 cells upon T cell receptor stimulation in the presence of cytokines such as TGF-b and IL-2 (3,4).…”

Section: Types Of Tregs: Phenotypingmentioning

confidence: 99%

Regulatory T Cells and Kidney Transplantation

Martín-Moreno

Tripathi

Chandraker

2018

CJASN

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The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4 cells that constitutively express high levels of the IL-2 receptor chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.

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Section: Types Of Tregs: Phenotypingmentioning

confidence: 99%

Regulatory T Cells and Kidney Transplantation

Martín-Moreno

Tripathi

Chandraker

2018

CJASN

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“…Tregs are dependent on signaling via CTLA4, and binding of belatacept to CD80/86 interferes with CTLA4. Therefore, the combination of belatacept with therapies that preserve Treg functionality, such as T-cell-depleting antibodies and mammalian target of rapamycin (mTOR) inhibitors could possibly lead to a reduced incidence of AR [4,56,57].…”

Section: Clinical Outcomes Of De Novo Use Of Belatacept In Kidney Tramentioning

confidence: 99%

“…Belatacept therapy influences the immunosuppressive function of Tregs [51][52][53][54][55]; therefore, the combination of belatacept with therapies that preserve Treg functionality, such as mTOR inhibitors, T-cell-depletion therapy, anti-CD40 antibodies, and adoptive therapy with Tregs could possibly lead to a more precise control of alloimmunity (Fig. 3) [56]. The combination of CTLA4/Ig and blockade of CD40/CD154 has not yet been tested in humans; however, in several animal transplant models, this combination produced long-term allograft survival [136][137][138][139][140].…”

Section: Future Directionsmentioning

confidence: 99%

Costimulation Blockade in Kidney Transplant Recipients

Zwan

Hesselink

Hoogen

et al. 2019

Drugs

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Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.

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“…[12][13][14][15][16][17] Currently, adoptive transfer of ex vivo expanded Tregs is a promising strategy to induce transplant tolerance and control graft rejection in kidney transplant recipients. 18,19 It has been investigated for safety and feasibility in phase I trials, i.e., the ONE (NCT02091232) and TRACT (NCT02145325). Identifying Treg-friendly agents from pharmacologic choices in multiple steps of kidney transplant management may also offer an attractive therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

“…Identifying Treg-friendly agents from pharmacologic choices in multiple steps of kidney transplant management may also offer an attractive therapeutic strategy. 19 Characterization of Tregs under various treatment conditions may help re ne current preventive measures or identify novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Effects of Desflurane and Sevoflurane Anesthesia on Regulatory T Cells in Patients Undergoing Living Donor Kidney Transplantation A Randomized Intervention Trial

Chutipongtanate

Prukviwat

Pongsakul

et al. 2020

Preprint

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Background: Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation.Methods: A prospective, randomized, double-blind trial in living donor kidney transplant recipients was conducted at a single center, tertiary-care, academic university hospital in Thailand during August 2015 – June 2017. Sixty-six patients were assessed for eligibility and 40 patients who fulfilled the study requirement were equally randomized and allocated to desflurane versus sevoflurane anesthesia during transplant surgery. The primary outcome included absolute changes of peripheral blood CD4+CD25+FoxP3+Tregs which measured by flow cytometry and expressed as the percentage of the total population of CD4+ T lymphocytes at pre-exposure (0-h) and post-exposure (2-h and 24-h) to anesthetic gas. P-value <0.05 denoted statistical significance.Results: Demographic data were comparable between groups. No statistical difference of peripheral blood Tregs between desflurane and sevoflurane groups observed at the baseline pre-exposure (3.6±0.4% vs. 3.1±0.4%; p=0.371) and 2-h post-exposure (3.0±0.3% vs. 3.5±0.4%; p=0.319). At 24-h post-exposure, peripheral blood Tregs was significantly higher in desflurane group (5.8±0.5% vs. 4.1±0.3%; p=0.008). Within group analysis showed patients receiving desflurane, but not sevoflurane, had 2.7% increase in peripheral blood Treg over 24-h period (p<0.001). Conclusion: This study provides the clinical trial-based evidence that desflurane induced peripheral blood Tregs increment after 24-h exposure, which could be beneficial in the context of kidney transplantation. Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future. Trial registration: ClinicalTrials.gov, NCT02559297. Registered 22 September 2015 - retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT02559297

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Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells

Cited by 30 publications

References 190 publications

Regulatory T Cells and Kidney Transplantation

Regulatory T Cells and Kidney Transplantation

Costimulation Blockade in Kidney Transplant Recipients

Effects of Desflurane and Sevoflurane Anesthesia on Regulatory T Cells in Patients Undergoing Living Donor Kidney Transplantation A Randomized Intervention Trial

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