Cloning Thymic Precursor Cells: Demonstration That Individual Pro-T1 Cells Have Dual T–NK Potential and Individual Pro-T2 Cells Have Dual αβ–γδ T Cell Potential

Thymic progenitors have the capacity to generate αβ T cells, γδ T cells, and NK cells. To determine whether these three lineages derive from a single precursor cell or from different precursors, a procedure was developed for cloning precursor cells from mouse embryonic thymus. The progeny of each pro-T cell clone were then tested for the potential to generate αβ, γδ, and NK cells. Of these precursor clones, about half displayed dual potential, developing into either T cells or NK cells, demonstrating the existence of a common T/NK precursor cell in the thymus. The other half of the clones were restricted to T cell development. No precursor clones were restricted to NK development. The common T/NK precursors were shown to be of the pro-T1 (CD25−) stage whereas the T-restricted precursors were shown to be of the later pro-T2 (CD25+) stage. Both αβ and γδ T cells were generated from all clones derived from either pro-T1 or -T2 precursors. This shows that commitment of a cell to the αβ versus γδ lineages does not precede rearrangement of the TCR genes (which occurs immediately after the pro-T2 stage).