Fig. 1.

Human T-cell development. Thymus-seeding progenitors (TSPs) that are derived from HSCs enter the thymus and differentiate into proT cells. The outcome of TCR rearrangements determines their fate as αβ T cells or γδ T cells. Successful rearrangement of the TCRβ leads to β-selection and subsequent emergence of CD4⁺ immature single-positive (ISP) cells. The CD4⁺ ISP then transitions into a CD4⁺CD8⁺ double-positive (DP) cell that has begun to rearrange its TCRα locus. DPs undergo apoptosis unless they receive a TCR-mediated survival signal established by interaction with self-HLA during positive selection. Following this process, DPs adopt either a CD4⁺CD8^– or CD4^–CD8⁺ fate and are termed single-positive (CD4 SP or CD8 SP) cells. Negative selection ensues within the thymus to delete any self-reactive cells. T cells migrate to the periphery and differentiate into effector cells after contact with APCs.