For a long time the thymus was considered to be an intrinsic primary steps towards tolerance occur within the thymus. To complete their differentiative programme, immature T cells component of the endocrine system but the endocrine model of cell-to-cell signalling failed to be fully validated in this receive signals from the thymic cellular microenvironment. Such signals may be emitted by thymic stromal cells ( like organ. With the discovery of its primary role in T-lymphopoiesis, the endocrine role of the thymus progresshormones or cytoldnes), or may result from direct interactions between cell adhesion molecules expressed on pre-T cells ively vanished from the literature, although the thymic influence was still believed to be mediated by a humoral (thymocytes) and thymic stromal cells (4, 5). During differentiation, immature T cells randomly rearrange the genes mechanism (1). However, in the past 15 years, the question of a neuroendocrine component in thymic physiology has coding for the segments of their TCR. Many of these random TCR combinations are orientated against self-antigens which resurfaced. From a number of studies, it now appears that the thymus is a crucial site for cross-talk between the neuroare expressed in the thymic microenvironment, then presented by proteins encoded in the major histocompatibility complex endocrine and immune systems, especially during foetal development (2). Thymic epithelial cells (TEC) and nurse cells (MHC). The interaction of self-reactive T cell clones with their cognate self-antigens is thought to lead to their negative (TNC) express a repertoire of neuroendocrine-related genes/ precursors, and thymic polypeptides may serve as signals selection, either by programmed cell death (apoptosis), or by developmental arrest. This process of thymic clonal deletion interacting with receptors on developing pre-T lymphocytes. This cryptocrine form of cell-to-cell signalling could play a was demonstrated with the use of mouse mammary tumour virus (MMTV )-encoded superantigens (6), and with transrole in T cell development and maturation. In addition, there is ample evidence that thymic neuroendocrine-related polygenic mice expressing a TCR specific for the male antigen (H-Y ) (7). Since the thymus does not express all the componpeptides behave as self-antigens which are presented to preT cells, and could induce the negative selection of T cells ents of the self-structure, this organ does not delete all potential autoreactive T cells. Consequently, the existence of bearing a randomly rearranged antigen receptor (TCR) orientated against endogenous neuroendocrine families (selfother mechanisms for developing tolerance (such as T cell anergy) at the periphery was postulated, and they were reactive T cells). The objective of this review is to expose most of the scientific arguments which support the important effectively shown to intervene in the process of immunological self-tolerance. Nevertheless, thymic clonal deletion of selfrole of the thymus in the education of T lymphocytes to recognize and tolerate neuroendocrine functions. reactive T cells is by far the most important mechanism involved in self-education of the immune system (8).