The immunological background to transplantation.
Organs are transplanted clinically to rectify an irreversible functional deficit but, unless donor and recipient are genetically identical, graft antigens will trigger a rejection response by the recipient. In the early part of this century, experiments on transplantation of tumours showed that there were strict limitations on the ability of tumour grafts to survive. These 'laws of transplantation' were confirmed by the elegant work of Sir Peter Medawar and colleagues who also showed that rejection is a systemic process governed by lymphocytes. The study of skin graft rejection in mice led to the discovery of the major histocompatibility complex (MHC) antigens, the function of which is to bind processed antigens and present them to T lymphocytes. T lymphocytes are pivotal in transplant rejection. The sensitization phase of rejection is due mainly to passenger leucocytes in the graft being recognised as foreign by the recipient's CD4+ T cells. The effector phase of rejection involves these activated recipient T cells entering the graft and locally producing cytokines. The rate of rejection depends on the relative contribution of the underlying immunological effector mechanisms. Our understanding of the role of T cells in transplant rejection has contributed much to knowledge on T cell physiology and function. The need to prevent rejection has also led to the development and use of new immunomodulating agents, approaches which have implications in the treatment of many other immunological disorders.
Haeney
M
M
Department of Immunology, Salford Royal Hospitals NHS Trust, Hope Hospital, UK.
D016207:Cytokines / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006648:Histocompatibility / Q000235:genetics; D006649:Histocompatibility Antigens / Q000276:immunology; D049673:History, 20th Century; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology; D014180:Transplantation / Q000266:history*; D014181:Transplantation Immunology
D016207:Cytokines; D006649:Histocompatibility Antigens