Islet Autoreactive CD8 T-cells in Type 1 Diabetes

Abstract

While differentiating T-cell autoreactivity against pancreatic islets between type 1 diabetic patients and nondiabetic control subjects has, over time, proven to be a difficult task, the ultimate challenge for cellular markers of this disease will involve the definition of immunological measures associated with disease progression and intervention. With the notion that type 1 diabetes is a T-cell–mediated autoimmune disease, it is therefore logical for investigators to direct research efforts toward studies of T-cells. However, relatively few studies associating T-cell autoreactivity with disease progression have been attempted (i.e., in comparison with efforts monitoring autoantibodies), and those that have been performed are largely limited to CD4 T-cells (1). Ever since the demonstration of their presence in insulitic lesions in the pancreas of patients at clinical onset of type 1 diabetes, CD8-positive cytotoxic T-cells have been implicated in the disease process (2). This association and its potential importance for disease was corroborated by the genetic predisposition of HLA class I loci for type 1 diabetes that is independent of linkage disequilibrium with HLA class II (3); a setting that implied the role of HLA class I with type 1 diabetes is more than guilt by genetic association alone (4). Theoretically, HLA class I–restricted CD8 T-cells could be the sole candidate …