Messengers of tolerance

The use of immunosuppressant drugs after organ transplantation has brought great success in the field of organ transplantation with respect to short-term outcome. However, major challenges (i.e., limited improvement of long-term survival, immunosuppressant toxicity, infections and carcinoma) demand alternate treatment approaches that minimizes the use of immunosuppressants. Interestingly, few studies have identified groups of transplant patients who developed operational tolerance and thereby keep their allograft without complications in absence of immunosuppressants. These rare groups of patients are of particular interest as study subjects for understanding mechanisms of graft tolerance that could be leveraged in future for inducing tolerance and for understanding mechanisms involved in improving long-term allograft outcomes. Also, biomarkers from these studies could benefit the larger transplant population by their application in immunosuppressant tailoring and identification of tolerant patients among patients with stably functioning allografts. This review compiles several gene expression studies performed in samples from tolerant patients in different solid organ transplantations to identify key genes and associated molecular pathways relevant to tolerance. This review is aimed at putting forth all this important work done thus far and to identify research gaps that need to be filled, in order to achieve the greater purpose of these studies.