Regulatory T Cells in Kidney Transplantation: New Directions?

Abstract

The contribution of regulatory T cells in the maintenance of kidney graft survival is of major interest. Although many experimental models suggest a role in the induction of graft tolerance, reproducing these findings in clinic is less clear. While modulation of the regulatory T cell response is a promising therapeutic concept in transplantation, a better understanding of function, phenotype and biology is needed to be able to optimally exploit these cells in order to induce graft tolerance. With this in mind, we review here the current understanding of the phenotypic-functional delineation of Tregs and how Tregs can contribute to graft survival. We highlight their potential role in long-term graft survival and kidney operational tolerance. We also discuss the mechanisms needed for the molecular development of regulatory T cells: A combination of FOXP3 molecular partners, epigenetic, metabolic, and posttranslational modifications are necessary to generate well-functioning regulatory T cells and maintain their core identify. We discuss how an improved understanding of these mechanisms will permit the identification of new potent therapeutic strategies to improve kidney graft survival. In this review, the authors summarize and discuss human regulatory T cells' role in long-term graft survival, new data regarding molecular pathways guiding the development, plasticity and stability of regulatory T cells, and how exploiting these mechanisms could be a potent therapeutic strategy to induce transplantation tolerance.