Figure 3. The transcription factor network that underlies T-cell lineage choice.

Th-POK (T-helper-inducing POZ/Kruppel-like factor) ‘seals’ CD4⁺ T-cell fate, which is specified by GATA-binding protein 3 (GATA3) and thymocyte selection-associated high-mobility group box (TOX), and represses CD8⁺ T-cell fate in part by repressing the expression of RUNX3 (runt-related transcription factor 3). In CD8⁺ T cells, RUNX3 maintains silencing of Th-POK expression, thereby repressing the CD4⁺ T-cell fate and irreversibly committing cells to the CD8 lineage. MYB is involved in promoting CD4 lineage choice, possibly by inducing the expression of GATA3 following T-cell-receptor activation.