A hypothetical model of thymic epithelial differentiation. If the high level of mitotic activity described by Gray et al for the MHC II^hi, CD80^hi medullary epithelial population is indicative of a transit-amplifying population, these cells may be less mature than and give rise to the MHC II^lo, CD80^lo population. According to this scenario, levels of tissue-restricted antigens (TRAs) and aire expression would be higher in the immature medullary epithelial compartment.