Histoire du thymus : d'un organe vestigial à la programmation de la tolérance immunitaire

This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus has been considered as a vestigial organ, and its role in T-lymphocyte differentiation has been proposed only in the 1960’s. Most recent studies attribute to the thymus an essential and unique role in the programming of central immunological self-tolerance. The basal mechanism implicated in this function is the transcription in thymic epithelium of genes encoding precursors of self-antigens. Processing of these latters leads to presentation of self-antigens by the major histocompatibility complex (MHC) machinery expressed by thymic epithelial and dendritic cells. During fetal life, this presentation drives negative selection of T-cell clones harboring receptors with high affinity for these complexes MHC/self-antigen. After birth, this presentation promotes the generation of regulatory T cells specific for these complexes. A number of studies, as well as the identification of Aire and Fezf2 genes, have shown that a thymus dysfunction plays a crucial role in the development of organ-specific autoimmunity.