Tolerance after Solid Organ and Hematopoietic Cell Transplantation

Abstract

Solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) have developed over the past 5 decades largely independent from each other despite sharing biologic principles, an almost identical repertoire of immunosuppressive (IS) drugs, and biologic response modifiers to overcome barriers of immune rejection between host and donor. Long-term graft function and recipient survival are the same primary endpoints for SOT and HCT. It is remarkable that allogeneic tissues can exhibit physiologic function in a host environment that may display disparate HLA antigens, blood type, and other immune response molecules. Long-term graft function after SOT in most cases requires life-long IS medications to prevent rejection in sharp contrast with HCT where most patients after 1 to 2 years post-HCT will be able to become independent of pharmacologic agents to avoid rejection or graft-versus-host-disease (GVHD) and therefore reach a clinical state of tolerance. The hallmark of tolerance is specific unresponsiveness between host and graft tissues in the absence of any IS drugs; however, an equally significant tenet is the prerequisite freedom from infections, reflecting immunocompetence that is identifiable by protective immune responsiveness against pathogens. The established mechanisms of transplantation tolerance include immunologic ignorance, central (thymic) and peripheral clonal deletion, anergy, and immune regulation [1]. In the following three sections, clinical and mechanistic studies highlight some of these mechanisms, as significant progress has been achieved after HCT, kidney, and liver transplantation. Excitingly, immunomodulatory strategies have recently translated into clinical success by combining HCT with living-donor SOT, using HCT as a means to achieve tolerance [2].