Original Article CD40–CD40 Ligand Interaction Activates Proinflammatory Pathways in Pancreatic Islets

Pancreatic islet transplantation is becoming an alternative to insulin therapy in patients suffering from brittle type 1 diabetes. A major obstacle to the procedure is the early graft loss caused by nonspecific inflammation at the site of implantation. We recently discovered that CD40, a member of tumor necrosis factor (TNF) receptor family, is ex-pressed in pancreatic -cells. CD40 expression in nonhema-topoietic cells is generally associated with inflammation. Therefore, we investigated the potential proinflammatory role of CD40 in human and nonhuman primate islets. Islet -cells responded to CD40L interaction by secreting inter-leukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein (MIP)-1, the latter a chemokine first reported to be produced by islets. Induc-tion of IL-8 and MIP-1 was confirmed at the transcrip