Medullary Thymic Epithelium: A Mosaic of Epithelial “Self”?

The thymus is organized into discrete subcapsular, cortical, and medullary environments that have been defined by the distribution of morphologically and phenotypically distinct populations of epithelial cells and other stromal cell constituents (1–5). T cell progenitor cells entering the thymus move in a centripetal fashion from the subcapsular region through the cortex to the medullary area during their maturation process. Proximal stages of thymocyte development thought to occur in the subcapsular and cortical compartments include expansion of the progenitor pool and expression of pre-TCR, which in turn selects thymocytes with a functional TCR-β chain to undergo further maturation and to become CD4⁺8⁺ (double positive, DP) thymocytes expressing low levels of TCR-α/β. Further development of DP thymocytes is dependent on recognition of MHC–peptide ligands expressed by cortical thymic epithelial cells. DP thymocytes expressing receptors of appropriate specificity for these ligands exhibit some phenotypic...