Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice

摘要: Abstract Tolerance to peripheral antigens is thought result from the inability of parenchymal tissue stimulate T cells--an that believed relate lack expression costimulatory signal(s) required for T-cell activation. To test this model, we generated transgenic mice expressing molecule B7-1 on B cells pancreas. We find islets these are immunogenic naive in vitro and vivo. Nonetheless, costimulator specifically beta do not develop diabetes, suggesting sufficient abrogate tolerance antigens. have reported tumor necrosis factor alpha subunit (TNF-alpha) expressed by leads a local inflammation but no islet destruction. Strikingly, however, combination due cytokine TNF-alpha results destruction diabetes.