title: Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway.
abstract: T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4-Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology. Abatacept and belatacept are clinically approved agents for the treatment of rheumatoid arthritis and renal transplantation, respectively. Future interventions may include selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4.
authors: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322.
authors: Andrew B
authors: AB
authors: Adams
authors: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322.
authors: Mandy L
authors: ML
authors: Ford
authors: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322 clarsen@emory.edu.
authors: Christian P
authors: CP
authors: Larsen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015551:Autoimmunity; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000502:physiology; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents