Fatal attraction: chemokines and type 1 diabetes.

Research discoveries within the past few years have dramatically reshaped our collective thought on the pathogenesis and natural history of type 1 diabetes (1). Many concepts once held as dogmas (e.g., B lymphocytes play no pathogenic role in type 1 diabetes; autoantibodies only serve as markers of the disease process; and Th1 cytokines are bad, in terms of the disease, whereas Th2 cytokines are good) have undergone major modification and, in some cases, have been completely reversed. It now appears that B lymphocytes play vital roles in presenting autoantigens necessary for disease development; that eliminating the maternal passage of antibodies can influence the subsequent rate of diabetes in offspring; and that the Th1/Th2 model has been saddled with so many “footnotes” regarding exceptions that it is now clear that initial hopes for a simple model to explain the immunopathogenesis of type 1 diabetes were, unfortunately, unrealistic. In addition to dogmas falling, many forgotten or overlooked aspects of the immune system as they apply to type 1 diabetes have found new life. Among such old (and even a few new) notions generating increased interest are antigen-presenting cells (e.g., dendritic cells, B lymphocytes), nontraditional T cells (e.g., NKT cells, NK cells), non–class I and –class II MHC molecules (e.g., CD1, MHC class I chain–related), cell receptors or intracellular pathways (e.g., toll, suppressor of cytokine signaling), and chemokines. A report by Kim and colleagues in this issue of the JCI investigates the role of chemokines and their receptors in T cell migration in a mouse model for human insulin-dependent diabetes (2).