Figure 1 Intrathymic T-cell differentiation Figure 1 | Intrathymic T-cell differentiation. a | T-cell progenitors enter the thymus via post-capillary venules in the cortico-medullary region of the thymus lobules and pass through distinct microenvironment regions: the outer cortex, followed by the inner cortex and finally the medulla. The thymocytes interact with cells in the thymus microenvironment such as cortical TECs, medullary TECs, dendritic cells and macrophages. Developing T cells also regulate the expression levels of different proteins, such as the TCR heterodimer, the CD3 complex, CD4, CD8, CD24, CD25, CD44, CD69 and CD62L, which can be used as markers to define a given stage of development within the organ. b | Cells of the thymus microenvironment interact via multiple mechanisms including: via the TCR and MHC/endogenous peptides (1), direct cell–cell interaction such as Notch or Delta-like protein 4 (2), the extracellular matrix, such as laminins and fibronectin, which bridge thymocytes to TEC via integrin-type membrane receptors (3), chemokines and other soluble moieties that activate G protein-coupled receptors (4) and via cytokines and peptidic hormones, such as IL-1, IL-7, growth hormone and prolactin (5). Abbreviations: DN, double negative; DP, double positive; MHC, major histocompatibility complex; TEC, thymus epithelial cell; TCR, T-cell receptor; SP, single positive. Savino, W. et al. (2015) Hormonal control of T‑cell development in health and disease Nat. Rev. Endocrinol. doi:10.1038/nrendo.2015.168