Costimulation couture: a designer approach to regulating autoimmunity.
Negative or inhibitory costimulatory pathways regulate T cell activation and play a role in peripheral tolerance. Targeting these pathways harnesses the physiologic mechanisms of regulating autoimmunity and could prove beneficial for the therapy of autoimmune diseases. However, attempts at targeting these pathways have been fraught with difficulties. In this issue of the JCI, Fife et al. describe a creative approach for targeting CTL-associated antigen 4 (CTLA-4) on activated T cells via genetically engineered B cells to prevent autoimmune diabetes in the NOD mouse (see the related article beginning on page 2252). Novel "designer" strategies targeting negative costimulatory pathways provide reasons for optimism in the search for a cure for devastating autoimmune diseases.
Ansari
Mohammed Javeed
MJ
Transplantation Research Center, Renal Division, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sayegh
Mohamed H
MH
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D003920:Diabetes Mellitus / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse