Identification of a T lineage-committed progenitor in adult blood.

With help of a hCD25 reporter controlled by pre-T cell receptor alpha (Ptcra) regulatory elements, T cell precursors were identified in peripheral blood. Sca-1(+)IL-7Ralpha(+)Flt3(-) precursors that were c-kit(lo)Thy-1(hi) generated T lineage cells when cultured on OP9-DL1 stromal cells and upon transfer into Rag2(-/-)Il2rg(-/-) mice. No B cells were generated in vivo and only few in vitro. These cells, which we call circulating T cell progenitors (CTP), were found at the same frequency in Foxn1(nu/nu) thymus-deficient mice and wild-type mice, indicating that they were pre- rather than postthymic. Inhibition of Notch-dependent transcription in vivo reduced the frequency of intrathymic early T cell progenitors (ETP), but not CTP, indicating that the latter are less Notch dependent. Thus, CTP represent T lineage-committed T cell precursors linking extrathymic with intrathymic lymphopoiesis in adult mice.