The effects of rapamycin on regulatory T cells: its potential time-dependent role in inducing transplant tolerance.

The immunosuppressive drug rapamycin (RAPA) has been used clinically to prevent graft rejection since 1999 because of its suppressive effects on T cell activation and proliferation. Recently, many studies have suggested that RAPA also has the potential to promote tolerance by driving the expansion of naturally occurring regulatory T (Treg) cells, and facilitating the de novo generation of induced Treg cells, which has aroused great interest in its potential ability to promote tolerance after transplantation. However, its effect on Treg cells remains controversial both in vitro and in vivo. Here, we systematically analyzed data on the effects of RAPA from both clinical and basic studies: (1) To compare its clinical effect with calcineurin inhibitors in transplant recipients, and discuss whether its effects on graft survival correlates with its effects on Treg cells. (2) To analyze the effects of RAPA on Treg cells from animal and in vitro studies, and to investigate whether the effects of RAPA on Treg cells was dependent on dosage and timing. (3) To discuss the mechanisms involved and how they might be applied to induce transplant tolerance.