Conventional immunosuppression and co-stimulation blockade.
Organ transplantation has become an accepted and successful therapeutic intervention for many patients with end-stage organ disease. Current conventional immunosuppressive regimens achieve very good short-term allograft survival but long-term outcomes are less than adequate. Furthermore, non-specific immunosuppression has its attendant side-effects including increased risks of malignancy and infection as well as drug-specific sequellae. With recent advances in the field of immunology, promising new therapies have arisen that could potentially eliminate lifelong drug therapy and promote indefinite acceptance of the donor tissue. Identification of co-stimulatory signals essential for T-cell activation has provided exciting new possibilities for controlling the alloimmune response. The compatibility of these new agents with proven conventional therapeutics has yielded mixed results. When used in combination, their immunosuppressive properties appear synergistic. However, if the goal of therapy is sustained, specific T-cell hyporesponsiveness, many conventional agents antagonize the effects of co-stimulatory blockade in several immune tolerance models.
Adams
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The Carlos and Marguerite Mason Transplantation Research Center, Department of Surgery, Emory University School of Medicine, 5105 Woodruff Memorial Research Building, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Pearson
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Larsen
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D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D060908:CTLA-4 Antigen; D004357:Drug Synergism; D006801:Humans; D018796:Immunoconjugates; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D023001:Transplantation Tolerance / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D023201:CD40 Ligand; D000069594:Abatacept