The thymus as an obligatory intersection between the immune and neuroendocrine systems: pharmacological implications.

Vincent Geenen received the MD (1982) and PhD (1987) degrees from the University of Liege Medical School in Belgium. He is currently Research Director for the National Fund of Scientific Research of Belgium (NFSR), Chairman of the Center of Immunology at University of Liege, Professor of Developmental Biology at Liege Faculty of Sciences, Professor of History of Biomedical Research at Liege Medical School, and Clinical Head in Endocrinology at Liege University Hospital. The recipient of several research awards in Belgium and Europe, he has given more than 90 invited lectures worldwide, authored or coauthored more than 140 papers and several book chapters, and coedited the book ‘Immunoendocrinology in Health and Disease’ (2004). He wrote the chapter ‘Thymus and T cells’ for the 2nd Edition of the Encyclopedia of Neuroscience on CD-ROM (Elsevier, 1998). His research focuses on thymus-dependent immunological self-tolerance, the role of a thymus dysfunction in the development of autoimmunity, the design of a thymus-based negative selfvaccine against type 1 diabetes, and immuneneuroendocrine interactions during embryo implantation and pregnancy. Dr. Vincent Geenen was the coordinator of the European FP6 Integrated Project Eurothymaide (2004–2008) entitled ‘Novel approaches in pathogenesis, diagnosis, and treatment of autoimmune diseases based on new insights into thymus-dependent self-tolerance, with special attention to type 1 diabetes’. Since 1995, his name is included in Who’s Who in the World, Who’s Who in Science and Engineering, and Who’s Who in Medicine and Health Care. Dr. Vincent Geenen holds memberships in the Endocrine Society, the American Association of Immunologists, the American Association of Diabetes, the International Federation of Neuroendocrinology, the European Association for the Study of Diabetes, the International Society of NeuroImmunoModulation and the European Neuroendocrine Association, among many organizations. Already in his famous side-chain theory (1900), P Ehrlich formulated the hypothesis that immune cells could express receptors susceptible to react against normal components of the body. In that case, however very improbable for him, he claimed that the organism should deploy specific mechanisms to escape from this difficulty (horror autotoxicus). In the second edition of ‘The Production of Antibodies’ (1949), F Macfarlane Burnet and F Fenner proposed the principle of self/nonself discrimination as the cardinal point of immune physiology, as well as the concept of self-markers for antigens encountered by precursors of immunocytes during embryonic life, to which thenceforth immunological tolerance could never be broken later in life. Autoimmunity, if this should occur, would then depend on ‘forbidden’ immune clones that later arose through somatic mutation. Since that time, self-tolerance has become a cornerstone of immune physiology, together with diversity, specificity and memory of the immune response. The absence or breakdown of self-tolerance is responsible for the progressive development of autoimmune diseases, either systemic (such as lupus erythematosus) or organ-specific (such as autoimmune endocrine diseases). All endocrine glands without exception may become deficient because of an autoimmune response directed against one or a few endocrine tissue-specific autoantigens. A legitimate question then is to understand why autoimmune pathogenic processes so frequently aggress endocrine tissues. The discovery of the intrathymic mechanisms responsible for the installation of central selftolerance has provided a number of answers to this important question. Among these answers, an important one concerns the true nature of self that is presented in the thymus to differentiating T cells during fetal life. Since its formulation some 60 years ago, self had been a seminal word coined in immunology’s language first as a fecund metaphor with some equivocal correlations to philosophy, psychology, and neurocognitive sciences. For unknown reasons, there were no serious attempts to elucidate the biochemical identity of self before a number of essential consecutive studies in the late 1980s and in the 1990s.