CRYPTOCRINE SIGNALING IN THE THYMUS NETWORK AND T-CELL EDUCATION TO NEUROENDOCRINE SELF-ANTIGENS

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroend ocrine and immune systems. This review presents the experimental obser vations which support a dual role in T cell selection played by the th ymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-rela ted precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, t hymic neuroendocrine-related polypeptides are a source of self-antigen s which are presented by the major histocompatibility system of the th ymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superim posible to the antigen presentation by dedicated presenting cells. Ins ulin-like growth factor-II (IGF-II) was identified as one dominant mem ber of the insulin family expressed by thymic epithelial and nurse cel ls. The intrathymic presentation of IGF-II or IGF-II derived self-anti gens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaborati on of a strategy for an efficient and safe prevention of insulin-depen dent diabetes.