New biologic immunosuppressive agents in transplantation.
Antigen-specific immunologic nonresponsiveness (tolerance) to alloantigens is a goal in transplantation. Most successful strategies of tolerance induction target the T cell. Activation of a quiescent T cell requires two different signals. Signal 1 is delivered when the T-cell receptor is engaged by foreign antigen presented by major histocompatibility complex molecules. Several potential pathways exist to deliver signal 2, which is also termed a costimulatory signal, although by far the best characterized pathway is through the T-cell co-receptor CD28. Blockade of either signal 1 or signal 2 may be sufficient to induce tolerance to alloantigens. Recent advances in knowledge of T-cell receptor-major histocompatibility complex interactions, in mechanisms of self-tolerance and in the identity and importance of costimulatory receptors and their ligands, have led to the development of various new strategies to block signals 1 and 2 using biologic agents. This review focuses on the most promising new modalities.
Gratiot-Deans
J
J
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0676.
Turka
L A
LA
D000818:Animals; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell