Pergamon A&,ances in Neuroimmunology Vol. 6, pp. 297-307, 1996 © 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0960-5428/96 832.00 PII: S0960-5428(97)00030-7 Interdependence of the endocrine and immune systems Mireille Dardenne*~f and Wilson SavinoJ; *CNRS URA 1461, Universit6 Paris V. H6pital Necker, 161 rue de S~vres, 75015 Paris, France +Laboratory on Thymus Research, Department of Immunology, Institute Oswaldo Cruz. Foundation Oswaldo Cruz, Rio de Janeiro, Brazil Keywords--Neuroimmunomodulation, hormones, cytokines, hypothalamus, anterior pituitary, thyroid, thymus, thymic epithelium. Summary The cross-talk involving the endocrine and immune systems is now largely established. These systems actually use similar ligands and recep- tors to establish a physiological intra- and inter- system communication circuitry, which apparently plays a relevant role in homeostasis (reviewed in Blalock, 1992). Accordingly, clas- sical hormones such as prolactin (PRL), growth hormone (GH) and even glucocorticoids (GC) can be produced by cells of the immune system, whereas a variety of cytokines, originally described as being produced by cells of the immune system, are synthesized and released by a variety of endocrine glands and nervous tissue. Moreover, specific receptors for such distinct molecular families can be detected in both the immune and endocrine systems. © 1997 Elsevier Science Ltd. All rights reserved. Neuroendocrine control of the immune system: the thymus paradigm Neuroendocrine control of immune function occurs at distinct levels of the immune system, tCorresponding author. including primary and secondary lymphoid organs, as well as sites of effector immunologi- cal activities. One of the lymphoid organs that has been widely studied in this regard is the thymus gland. Within this compartment of the immune system, bone marrow-derived T cell precursors undergo a complex process of matura- tion that includes selection of the T cell repertoire, with positively selected cells eventually migrat- ing to the T-dependent areas of peripheral lym- phoid organs, where they will further expand (reviewed in van Ewijk, 1991; Owen and Moore, 1995). Importantly, key events of intrathymic T cell differentiation are driven by the influence of the thymic microenvironment, a tridimensional network composed of various cell types includ- ing epithelial cells, dendritic cells and macro- phages, as well as extracellular matrix elements (reviewed in Boyd et al., 1993; Savino et al., 1993). The thymic microenvironment controls thymocyte migration and differentiation through (1) secretion of a variety of polypeptides includ- ing thymic hormones and cytokines (reviewed in Bach, 1983; Haynes et al., 1990); and (2) cell- cell contacts, such as the interactions occurring through classical adhesion molecules (reviewed 297