The c-kit(+) maturation pathway in mouse thymic T cell development: Lineages and selection

Positive selection of T cells begins with TCR alpha beta(lo) thymic progenitors. Here, we show that the most efficient TCR(lo) progenitors are c-kit(+) with intermediate levels of CD4 and CD8 (DPint). Positive selection of DPint TCR(lo) c-kit(+) cells results in TCR(med) CD69(+) c-kit(+) transitional intermediates that show increased TCRV beta frequencies to selecting superantigen (SAg) that are committed to the CD4 or CD8 pathway. The cells on the c-kit(+) maturation pathway maintain Bcl-2 expression. Most DPint c-kit(+) progenitors fail positive selection, and become DPhi c-kit(+) cells that lose Bcl-2 expression. Some DPhi c-kit blast cells can be salvaged to produce mature single-positive (SP) cells. DPint c-kit(+) maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers.