Identification of an early T cell progenitor for a pathway of T cell maturation in the bone marrow

We have identified a rare (≈0.05–0.1%) population of cells (Thy-1(hi)CD16(+)CD44(hi)CD2(−)TCRαβ(−)B220(−)Mac-1(−)NK1.1(−)) in the adult mouse bone marrow that generates CD4(+) and CD8(+) TCRαβ(+) T cells after tissue culture for 48 hr in the presence of Ly5 congenic marrow cells. The essential stages in the maturation of the progenitors were determined; the stages included an early transition from CD2(−)CD16(+)CD44(hi)TCRαβ(−) to CD2(+)CD16(int/−)CD44(int/−)TCRαβ(−) cells, and a later transition to CD4(+)CD8(+)TCRαβ(+) double-positive T cells that rapidly generate the CD4(+) and CD8(+) single-positive T cells. The maturation of the progenitors is almost completely arrested at the CD2(+)TCRαβ(−) stage by the presence of mature T cells at the initiation of cultures. This alternate pathway is supported by the marrow microenvironment; it recapitulates critical intermediary steps in intrathymic T cell maturation.