THYMIC EXPRESSION OF NEUROENDOCRINE SELF-PEPTIDE PRECURSORS - ROLE INT-CELL SURVIVAL AND SELF-TOLERANCE

For a long time the thymus was considered to be an intrinsic component of the endocrine system but the endocrine model of cell-to-cell signa lling failed to be fully validated in this organ. With the discovery o f its primary role in T-lymphopoiesis, the endocrine role of the thymu s progressively vanished from the literature, although the thymic infl uence was still believed to be mediated by a humoral mechanism (1). Ho wever, in the past 15 years, the question of a neuroendocrine componen t in thymic physiology has resurfaced. From a number of studies, it no w appears that the thymus is a crucial site for cross-talk between the neuroendocrine and immune systems, especially during foetal developme nt (2). Thymic epithelial cells (TEC) and nurse cells (TNC) express a repertoire of neuroendocrine-related genes/precursors, and thymic poly peptides may serve as signals interacting with receptors on developing pre-T lymphocytes. This cryptocrine form of cell-to-cell signalling c ould play a role in T cell development and maturation. In addition, th ere is ample evidence that thymic neuroendocrine-related polypeptides behave as self-antigens which are presented to pre-T cells, and could induce the negative selection of T cells bearing a randomly rearranged antigen receptor (TCR) orientated against endogenous neuroendocrine f amilies (self-reactive T cells). The objective of this review is to ex pose most of the scientific arguments which support the important role of the thymus in the education of T lymphocytes to recognize and tole rate neuroendocrine functions.