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Review
. 2023 Jan 16;24(2):1752.
doi: 10.3390/ijms24021752.

Treg Therapy for the Induction of Immune Tolerance in Transplantation-Not Lost in Translation?

Nina Pilat  1   2 , Romy Steiner  1   2 , Jonathan Sprent  3   4
Affiliations
Review

Treg Therapy for the Induction of Immune Tolerance in Transplantation-Not Lost in Translation?

Nina Pilat et al. Int J Mol Sci. .

Abstract

The clinical success of solid organ transplantation is still limited by the insufficiency of immunosuppressive regimens to control chronic rejection and late graft loss. Moreover, serious side effects caused by chronic immunosuppressive treatment increase morbidity and mortality in transplant patients. Regulatory T cells (Tregs) have proven to be efficient in the induction of allograft tolerance and prolongation of graft survival in numerous preclinical models, and treatment has now moved to the clinics. The results of the first Treg-based clinical trials seem promising, proving the feasibility and safety of Treg therapy in clinical organ transplantation. However, many questions regarding Treg phenotype, optimum dosage, antigen-specificity, adjunct immunosuppressants and efficacy remain open. This review summarizes the results of the first Treg-based clinical trials for tolerance induction in solid organ transplantation and recapitulates what we have learnt so far and which questions need to be resolved before Treg therapy can become part of daily clinical practice. In addition, we discuss new strategies being developed for induction of donor-specific tolerance in solid organ transplantation with the clinical aims of prolonged graft survival and minimization of immunosuppression.

Keywords: regulatory T cells; tolerance; transplantation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Differentiation dynamics and plasticity of (regulatory) T cells. cm: central memory; em: effector memory; e: effector; p: peripheral (created with biorender.com).
Figure 2
Figure 2
Different approaches for in vitro expansion of Tregs. Engineering approaches are supposed to increase specificity and feasibility. PBMCs: peripheral blood mononuclear cells; FACS: fluorescence-activated cell sorting; MACS: magnetic-activated cell sorting; APC: antigen-presenting cell; TCR: T cell receptor; CAR: chimeric antigen receptor (created with biorender.com).
Figure 3
Figure 3
Approaches for in vivo expansion of Tregs (created with biorender.com).
See this image and copyright information in PMC

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References

    1. Billingham R.E., Brent L., Medawar P.B. Actively acquired tolerance of foreign cells. Nature. 1953;172:603–606. doi: 10.1038/172603a0. - DOI - PubMed
    1. Slepicka P.F., Yazdanifar M., Bertaina A. Harnessing Mechanisms of Immune Tolerance to Improve Outcomes in Solid Organ Transplantation: A Review. Front. Immunol. 2021;12:688460. doi: 10.3389/fimmu.2021.688460. - DOI - PMC - PubMed
    1. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995;155:1151–1164. doi: 10.4049/jimmunol.155.3.1151. - DOI - PubMed
    1. Shevach E.M. From vanilla to 28 flavors: Multiple varieties of T regulatory cells. Immunity. 2006;25:195–201. doi: 10.1016/j.immuni.2006.08.003. - DOI - PubMed
    1. Abbas A.K., Trotta E., Simeonov D.R., Marson A., Bluestone J.A. Revisiting IL-2: Biology and therapeutic prospects. Sci. Immunol. 2018;3:eaat1482. doi: 10.1126/sciimmunol.aat1482. - DOI - PubMed

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