Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs

Recent reports indicate that genes with tissue-restricted expression, inclu ding those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or IC A512), are transcribed in the thymus. The reported modulation of diabetes s usceptibility by genetically determined differences in thymic insulin level s and studies in transgenic mice provide correlative and functional evidenc e that thymic expression of peripheral proteins is crucial for immunologica l self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express in sulin and other self-antigens in the human thymus. We find that the human t hymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, m ainly localized in the medulla, and we demonstrate such cells also in perip heral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifi es these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages, These cells often appear surrounded by apoptotic ly mphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existenc e of, and define the tissue distribution and phenotype of, a novel subset o f APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.