Transplant immunology.
The immune response to an allogeneic transplanted organ is T-cell dependent. It is governed partially by the context in which the T-cell encounters the antigen and can range from apoptosis, anergy, and neglect to full activation. The current armamentarium of immunosuppressive agents acts to inhibit the various steps of this T-cell activation pathway; at the level of the T-cell receptor (monoclonal antibodies such as OKT3), intracellular signally (calcineurine-inhibitors), DNA synthesis (azathioprine), or to cause lymphocyte depletion (ATG, ALG). Most protocols use a combination of agents for induction and maintenance immunosuppression. Although successful in preventing and treating allograft rejection, they are not without side effects. With improved patient and graft survival rates, adverse events such as hypertension, nephrotoxicity, hyperglycaemia, and lymphoproliferative disease become increasingly important issues. Newer drugs (IL-2 receptor antagonists, mycophenolate mofetil, rapamycin) have been introduced in an attempt to spare or avoid these adverse effects. Inducing graft tolerance and long-term drug-free survival is the goal of transplant immunologists. Postulated mechanisms include clonal deletion, anergy, and immunoredirection. Although a number of methods have been tested experimentally, none has been proven to induce tolerance for routine clinical use. Immunosuppression remains the cornerstone of the success of organ transplantation. Until investigators are able to induce tolerance in their transplant recipients or develop a tolerance assay, they would need to continue to tailor their immunosuppressive therapy according to the risk profile of the individual recipient.
Aw
Marion M
MM
Department of Paediatrics and Liver Transplant Unit, National University Hospital, Singapore.
D006084:Graft Rejection; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents; D016377:Organ Transplantation / Q000502:physiology; D011948:Receptors, Antigen, T-Cell; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell