Control of Early T Cell Development by Notch and T Cell Receptor Signals

αβ and γδ T cells develop from a common progenitor cell in the thymus. Commitment of multipotent thymic seeding progenitors to the T lineage is induced by signals transduced by the Notch transmembrane receptor upon encounter of Notch ligands in the thymus. Subsequent commitment of immature T cell progenitors to the αβ or γδ T cell lineages is instructed by signals transduced by the multisubunit T cell antigen receptor (TCR) complex. The pre-TCR and γδ TCR complexes instruct progenitors to adopt the αβ and γδ fate, respectively, and the nature of the signal that these receptors transduce is a key determinant in this process. The pre-TCR generates weak or transient signals that require assistance from the Notch receptor to direct adoption of the αβ T cell fate. The γδ TCR, on the other hand, produces a signal that is sufficiently strong or prolonged that it can induce adoption of the γδ cell fate without assistance from Notch. The γδ TCR also plays a crucial role in equipping developing γδ T cells with the ability to produce particular cytokines or effector fates. Weak γδ TCR signals equip γδ T cells to produce the cytokine interleukin-17 (IL-17), while stronger TCR signals promote the ability to produce interferon-γ (IFNγ). The strongest TCR signals equip progenitors to be fast-acting and respond to the presence of activating cytokines, and these cells are referred to as innate-like γδ T effector cells.