Watching clonal deletion in action

T cells that recognize self antigens are commonly eliminated in the thymus. Such clonal deletion represents an important protection from autoimmune disease, but its effects are limited to proteins that are expressed within the thymus and can be presented to developing T cells, largely by thymic dendritic cells (DCs) or macrophages. Hence, it is not surprising that many autoantigens are proteins with limited distribution, for which this mechanism of central tolerance cannot be used. However, over the last several years, it has become clear that proteins whose physiological role is elsewhere are nevertheless expressed in the thymus. Pugliese and coworkers show that thymic DCs express and present several major pancreatic proteins that are known autoantigens in Type I diabetes. Remarkably, these self-antigen presenting DCs can be seen in histological preparations surrounded by T cells that are undergoing apoptosis, presumably because they are specific for the self-epitope presented by the neighboring DC