Drugs

, Volume 75, Issue 16, pp 1843–1852 | Cite as

Pharmacologic Targeting of Regulatory T Cells for Solid Organ Transplantation: Current and Future Prospects

  • Kassem Safa
  • Sindhu Chandran
  • David Wojciechowski
Leading Article
First Online:

Abstract

The last three decades have witnessed significant advances in the development of immunosuppressive medications used in kidney transplantation leading to a remarkable gain in short-term graft function and outcomes. Despite these major breakthroughs, improvements in long-term outcomes lag behind due to a stalemate between drug-related nephrotoxicity and chronic rejection typically due to donor-specific antibodies. Regulatory T cells (Tregs) have been shown to modulate the alloimmune response and can exert suppressive activity preventing allograft rejection in kidney transplantation. Currently available immunosuppressive agents impact Tregs in the alloimmune milieu with some of these interactions being deleterious to the allograft while others may be beneficial. Variable effects are seen with common antibody induction agents such that basiliximab, an IL-2 receptor blocker, decreases Tregs while lymphocyte depleting agents such as antithymocyte globulin increase Tregs. Calcineurin inhibitors, a mainstay of maintenance immunosuppression since the mid-1980s, seem to suppress Tregs while mammalian targets of rapamycin (less commonly used in maintenance regimens) expand Tregs. The purpose of this review is to provide an overview of Treg biology in transplantation, identify in more detail the interactions between commonly used immunosuppressive agents and Tregs in kidney transplantation and lastly describe future directions in the use of Tregs themselves as therapy for tolerance induction.

Keywords

Tacrolimus Rapamycin Acute Rejection Alemtuzumab Abatacept 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Compliance with Ethical Standards

Conflict of interest

K. Safa has no conflicts to report. S. Chandran has received grant support from BMS. D. Wojciechowski has received grant support from Novartis, BMS, Oxford Immunotec and Qiagen.

Funding

No sources of funding were used to support the writing of this review.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Kassem Safa
    • 1
  • Sindhu Chandran
    • 2
  • David Wojciechowski
    • 1
  1. 1.Division of Nephrology and Transplant CenterMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Division of Nephrology, Department of MedicineUniversity of California San Francisco Medical centerSan FranciscoUSA

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