title: Immune Exhaustion and Transplantation.
abstract: Exhaustion of lymphocyte function through chronic exposure to a high load of foreign antigen is well established for chronic viral infection and antitumor immunity and has been found to be associated with a distinct molecular program and characteristic cell surface phenotype. Although exhaustion has most commonly been studied in the context of CD8 viral responses, recent studies indicate that chronic antigen exposure may affect B cells, NK cells and CD4 T cells in a parallel manner. Limited information is available regarding the extent of lymphocyte exhaustion development in the transplant setting and its impact on anti-graft alloreactivity. By analogy to the persistence of a foreign virus, the large mass of alloantigen presented by an allograft in chronic residence could provide an ideal setting for exhausting donor-reactive T cells. The extent of T cell exhaustion occurring with various allografts, the kinetics of its development, whether exhaustion is influenced positively or negatively by different immunosuppressants, and the impact of exhaustion on graft survival and tolerance development remains a fertile area for investigation. Harnessing or encouraging the natural processes of exhaustion may provide a novel means to promote graft survival and transplantation tolerance.
authors.affiliation: Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, Medical Research Council Centre for Transplantation, Faculty of Life Sciences and Medicine, King's College London University, King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Fueyo
authors.affiliation: Division of Transplant Surgery, Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016377:Organ Transplantation; D023001:Transplantation Tolerance / Q000276:immunology*
keywords: T cell biology; immunobiology; immunosuppression/immune modulation; tolerance; tolerance: mechanisms; translational research/science