Influence of pharmacological immunomodulatory agents on CD4(+)CD25(high)FoxP3(+) T regulatory cells in humans

Abstract

T regulatory cells (Tregs) play a critical role in the immunologic tolerance to the graft in transplantation. Thus, due to their immunosuppressive capability, ex vivo expanded Tregs may be used as a cellular therapy and an attractive novel strategy to control chronic rejection and eliminate need for lifelong pharmacological immunosuppression. Since Treg therapy is still in its infancy, initially Tregs still need to be applied in combination with pharmacological agents to prevent rejection. Fortunately, some of the medications have been shown to enhance the function and number of Tregs. In the clinic, different immunosuppressive regimens are used for individual patients for different types of organ transplantation. In this review, we present the most commonly used pharmacological agents for immunosuppression and discuss how they affect the Treg population. It is extremely difficult to dissect the effect of single agent on Tregs population in clinical settings since usually the combination of several medications is applied at the same time for graft protection. Nevertheless, experimental and clinical data indicate that thymoglobulin as immunosuppressive induction and mTOR inhibitors as immunosuppressive maintenance agents have the most beneficial effect on Treg population in the blood. Among supplemental agents promoting Tregs, anti-TNFα preparations have been in clinical use (in autoimmune diseases) for many years, so they are optimal candidates for testing in transplant settings in combination with Treg based cellular therapy.