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.
Krueger
Andreas
A
Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
von Boehmer
Harald
H
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D053645:Interleukin-2 Receptor alpha Subunit; D051880:Receptors, Notch