Immunosenescence in Kidney Transplant Recipients

Abstract

The term immunosenescence refers to the collective effects of aging on the immune system, which involves both the innate and the adaptive immunity and plays a dominant role in patients' morbidity and mortality. Senescent T lymphocytes are in a state of replicative arrest and have several unique features: they typically lack costimulatory molecules, they express shortened telomeres, and they have the capacity to produce large amounts of proinflammatory cytokines. The B-lymphocyte compartment and the cells of the innate immune system also demonstrate important changes due to aging. The immunosenescent phenotype in humans is believed to be associated with chronic antigenic stimulation that occurs, among others, in allotransplantation due to constant exposure to donor alloantigens. Kidney transplantation is the preferred treatment for all patients with end-stage renal disease, yet it places the immune system in a unique and aberrant state. On one hand, immunosenescence could be an important determinant of tolerance to the transplant. On the other hand, the immunosenescent phenotype might contribute to the increased morbidity and mortality of patients with kidney transplantation. Several studies have assessed the immunosenescent phenotype mainly of T lymphocytes, either before and after kidney transplantation, by comparing different immunosuppressants or in conjunction with age, the occurrence of infection, or cancer. Animal studies have provided insight into the possible implications of the immunosenescence of the graft, while senolytics might be an attractive therapeutic option in the future. In this narrative review, we discuss the existing bibliography about immunosenescence in the context of kidney transplantation.