Schematic of T-cell development.

The earliest T-lineage cell is the TN CD44+CD25⁻ pro-T1 thymocyte. This cell can also give rise to B cells, NK cells, and dendritic cells. The next stage is a CD44⁺CD25⁺pro-T2 cell, which can give rise to T cells and probably dendritic cells. This stage involves proliferation in response to IL-7 and SCF. Rearrangement of the β, γ, and δ TCR chains begins at the end of this stage and is associated with diminished proliferation. The CD44⁻CD25⁺ and CD44⁻CD25⁻ stages are characterized by the completion of rearrangement and the death of thymocytes that fail to undergo successful rearrangement, followed by a period of expansion. Thymus-derived γδ T cells arise from the CD44⁻CD25⁺ and possibly the CD44⁻CD25⁻ stages. IL-7Rα chain is expressed throughout the TN stage, contributing to proliferation, survival, and rearrangement (at least for the δ locus) as described in more detail in “Developing T cells.” TN thymocytes comprise approximately 5% of the thymocyte fraction. Positive selection occurs during the DP stage, resulting in the death of most thymocytes and in self-MHC restriction. IL-7Rα expression is down-regulated during this stage. Rearrangement of the TCR-α component takes place during the DP stage. Clonal deletion of thymocytes expressing self-reactive TCRs begins toward the end of the DP stage and probably continues through the early SP stage. IL-7Rα chain is re-expressed at the SP stage and remains, at some level, throughout the life of a mature T cell. Eighty percent of thymocytes are DP, and 15% are SP.