Long-Term Survival of Xenogeneic Pancreatic Islet Grafts Induced by CTLA4lg

Antigen-specific T cell activation depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (Ig) G1 Fc region (CTLA4Ig) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4Ig therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7 + antigen-presenting cells. In addition, CTLA4Ig induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.