Impact of mammalian target of rapamycin inhibition by everolimus on peripheral blood αβ and γδ T lymphocytes in renal transplant recipients (TRAN1P.875)

Abstract

The kidney is an essential organ necessary for the human body to discharge harmful toxins and is imperative for filtering blood. According to the Centers for Disease Control and Prevention, kidney disease is the eighth leading cause of death in the United States. Diabetes and hypertension are two major factors that influence kidney function, which can consequently lead to end-stage renal disease. The primary method of treatment for end-stage renal disease is kidney transplantation, which requires a regimen of immunosuppressant drugs to prevent allograft rejection. Previously, our lab has shown that administration of the immunosuppressant drug, sirolimus a mammalian target of rapamycin inhibitor, also known as mTOR, impairs skin homeostasis and wound repair. To further understand the mechanism behind this adverse effect of mTOR suppression, we examined renal transplant recipients who were administered the sirolimus derivative everolimus. The number and activation of αβ and γδ T cells in the blood of patients administered everolimus were compared to a control group of patients not administered everolimus. Several of these T cell populations, including Vγ9Vδ2 T cells, have been previously displayed to home to sites of tissue damage to improve wound repair. This data explores which T lymphocyte populations require mTOR to maximize function in transplant recipients with implications in tissue repair and graft rejection.