Identification of a T lineage-committed progenitor in adult blood

Immunity. 2007 Jan;26(1):105-16. doi: 10.1016/j.immuni.2006.12.004. Epub 2007 Jan 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Lineage / immunology*
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphopoiesis / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, Notch / immunology
  • Receptors, Notch / metabolism
  • Regulatory Elements, Transcriptional
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology

Substances

  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Notch