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

Kassem Safa, Sindhu Chandran, David Wojciechowski

Research output: Contribution to journalReview article

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1843-1852
Number of pages10
JournalDrugs
Volume75
Issue number16
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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Organ Transplantation
Regulatory T-Lymphocytes
Immunosuppressive Agents
Kidney Transplantation
Allografts
Maintenance
Antilymphocyte Serum
Antibodies
Interleukin-2 Receptors
Sirolimus
Immunosuppression
Transplantation
Lymphocytes
Transplants
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacologic Targeting of Regulatory T Cells for Solid Organ Transplantation : Current and Future Prospects. / Safa, Kassem; Chandran, Sindhu; Wojciechowski, David.

In: Drugs, Vol. 75, No. 16, 01.11.2015, p. 1843-1852.

Research output: Contribution to journalReview article

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