Viewpoint: therapeutic implications of CTLA-4 compartmentalization.
Understanding the regulatory events involved in the activation and inactivation of T cells is crucial to develop therapeutic approaches for autoimmune diseases and for organ transplantation. Co-stimulatory signals delivered through the CD28 receptor and inhibitory signals through CTLA-4 are required for the proper modulation of T cell responses and the induction and maintenance of peripheral tolerance. Manipulation of these signals is emerging as a potential strategy to prevent allograft rejection in different animal models. Recent data on the compartmentalization and the structural features of CTLA-4 within T cells provides critical information not only on the molecular basis of T cell inactivation by CTLA-4, but also on the key requirements for the successful development of therapeutic strategies targeting this molecule.
Baroja
Miren L
ML
The John P. Robarts Research Institute, Department of Microbiology, The University of Western Ontario, London, Ontario, Canada N6A 5K8.
Madrenas
Joaquín
J
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002451:Cell Compartmentation; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human