title: Advances in transplantation tolerance.
abstract: Immunosuppressive drugs developed in the past two decades have improved the short-term survival of organ allografts, but tolerance has not been achieved and almost all transplant recipients continue to require drugs throughout life. Graft rejection arises from the cognate interaction of T cells with antigen-presenting cells, the recognition of alloantigen through the T-cell receptor, and the delivery of accessory stimulation signals. Once activated by the specific antigen, replicating T cells die if they are re-exposed to the same antigen. Since depletion of antigen-activated T cells is one critical mechanism of transplantation tolerance, drugs such as ciclosporin that interfere with activation-induced T-cell death could inhibit tolerance, whereas drugs such as mycophenolate mofetil, that induce the death of activated T cells, could facilitate tolerance. Other tolerance mechanisms depend on inactivation rather than elimination of allograft reactive T cells. When antigen recognition occurs without costimulation through the CD28 and CD154 accessory receptors, or in absence of cell division, T cells become unresponsive. Thus, inhibitors of CD28 and CD154, and inhibition of T-cell division by rapamycin promotes transplantation tolerance.
authors: Human Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: X
authors: X
authors: Yu
authors: P
authors: P
authors: Carpenter
authors: C
authors: C
authors: Anasetti
mesh_terms: D018106:CD28 Antigens / Q000187:drug effects; D023201:CD40 Ligand / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D023201:CD40 Ligand