Autoreactive T cells in human type 1 diabetes

Studies on T-cell targets reveal the potential for disease-related and human leukocyte antigen (HLA) allele-related peptide epitopes to be identified, using current technology. Studies using these epitopes, coupled with T-cell clone analyses, provide strong evidence that circulating autoreactive T cells are available for analysis in the peripheral blood of patients with type 1 diabetes (T1D). Functional examination of T-cell clones and T cells in the blood indicate that many responder cells have a Th1-like, pro-inflammatory phenotype. T-cell assay technology is becoming more refined and sensitive, but there is unlikely to be a "quick fix" solution to the direct and reliable enumeration of autoreactive T cells in peripheral blood. This article reviews literature that suggests that there can be no substitute for the quality of information to be gained from the systematic analysis of T-cell clones and their epitopes. It is likely, therefore, that the ability to combine HLA-restricted epitope discovery with assays using functional read-outs, such as cytokine production, in carefully defined populations of patients with T1D, will be ultimately rewarding.