Regulatory T cells in renal transplantation and modulation by immunosuppression

The poor long-term graft survival rate counteracts the important advance that transplantation is for end-stage renal disease patients. This is mainly due to the employment of immunosuppression that inhibits nonspecifically the alloimmune response to avoid graft rejection, but, at the same time, brings a number of adverse effects leading to chronic rejection. Thus, the major goal in transplantation is to reach an absence of immune response towards donor alloantigens without the need of long-term immunosuppressant drugs. In recent years, regulatory T cells, mainly those with a CD4CD25FOXP3 phenotype (named as Tregs), have demonstrated an inhibitory effect on immune responses against donor alloantigens. As a consequence, they are a potential tool in the development of transplant tolerance in vivo. Most of the evidence comes from experimental models, although recent works address the role of Tregs in the clinical arena of transplantation. In such a setting, the coexistence of immunosuppression in almost 100% patients is an essential factor to consider. Recent findings show that different drugs favor the induction and maintenance of Tregs in renal transplant recipients. Among them, mammalian target of rapamycin inhibitors seem to better promote the development of Tregs at present. The present work reviews all the evidence published up to date about Tregs in human renal transplantation with a special focus on the effect of clinical protocols of immunosuppression.