The generation and fate of thymocytes

In the adult thymus the majority of thymocytes are at a non-proliferating end stage, during which 3% of all CD4+CD8+ cortical thymocytes are selected on the basis of appropriate T-cell antigen-receptor (TcR) specificity to become CD4-CD8+ or CD4+CD8- mature thymocytes. The selected mature cells gradually emigrate to the periphery. The 97% unselected, or positively rejected, CD4+CD8+ thymocytes die in the thymus. This 3-day end stage is, however, the product of around 2 weeks of proliferation by less mature thymocytes, which gives about a 10(5)-fold expansion from the hundred prothymocytes estimated to seed the thymus each day. Rearrangement and expression of TcR genes and a sequence of changes in surface antigens occurs during this prolonged period. Two sequential waves of expansion and differentiation appear to be involved. The first, about 1 week long, involves the less than 0.1% of thymocytes which still resemble the prothymocyte; this leads via a non-dividing interval to the second 1-week stage involving the 3% of CD4-CD8- thymocytes and then the CD4+CD8+ blasts.