HEB in the Spotlight: Transcriptional Regulation of T-Cell Specification, Commitment, and Developmental Plasticity

Figure 6

Development of T versus tNK cells in the thymus. DN1 cells enter thymus at the corticomedullary junction (CMJ). This area is low in DL4 but high in DL1 ligand; in addition, there is a low amount of IL-7 and SCF dispersed throughout a thymus. DN1c and DN1d cells may be progenitors to a small number of B cells generated intrathymically. DN1a and DN1b cells represent canonical early T-cell progenitors (ETPs), which migrate to the inner cortex, the area of high DL4 ligand concentration. In response to Notch signalling, ETPs turn on many of the T-lineage specific genes and develop into DN2 cells. At the DN3 stage, the cells rearrange TCRβ genes and undergo β-selection, thus expanding and taking up most of the space in the outer cortex. This is disadvantageous for those DN3 cells that have not rearranged TCRβ, which may give rise to the thymic NK cells. Thus, a small percentage of NK cells may be generated in a thymus, mostly from the DN1e progenitors, which are likely to remain near the CMJ region where the DL4 ligands are low and the IL-7 concentration is sufficient for the thymic NK cell development.