Immune system cells (lymphocytes, dendritic cells, phagocytic cells) originate from the hematopoietic system, which in adulthood is located in the bone marrow.
T lymphocytes differentiate in the thymus through a series of stages involving cell migration, division, differentiation/specification, selection and migration of mature cells to secondary lymphoid organs. The thymus organ is generated from epithelial stem cells located in the pharyngeal endoderm. The key genes in this program have been identified. The progenitors, according to a molecular program that has yet to be elucidated, give rise to the epithelial cells of the cortex and medulla. Differentiation of the thymus involves cross-talk between lymphocyte precursors, dendritic cells and epithelial cells. A detailed understanding of these intercellular communications is a major challenge, one aim of which could be the ability to amplify or regenerate thymic functions. However, the thymus is endowed with a time clock that leads to its involution, a phenomenon whose molecular mechanisms we do not yet know, but which may have been selected during evolution as a safeguard against excessive risks of lymphocyte leukemogenesis and/or autoimmunity. The key factors that induce the specification of T and B cell precursors and their hierarchical arrangement are now known; their action is progressive during thymic lymphopoiesis (T cells) or medullary lymphopoiesis (B cells). Low-affinity "positive" selection events (through recognition of low-affinity self peptides) followed by "negative" selection events (through recognition of high-affinity self peptides) have attracted the attention of immunologists for many years. In particular, they have led to the identification of the role of the AIRE protein in the "ectopic" induction of tissue protein expression in medulla cells. This enables a wide range of self peptides to be presented to T lymphocytes. T-cell production in humans takes over three months, a long time whose stages - as analyzed in mice by vital function microscopy - are still only imperfectly understood. This is an essential question, which could help reduce the risks inherent in the absence of T-cell production in humans during a long phase after allogeneic hematopoietic stem cell transplantation.
