Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene

Nat Immunol. 2002 May;3(5):489-96. doi: 10.1038/ni778. Epub 2002 Apr 1.

Abstract

A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4(lo)CD8(-)CD25(-)CD44(+)c-Kit(+) cells that expressed elevated levels of Notch-1 mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19(-), B220(+), Thy1(+) and CD4(+) cells. Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Flow Cytometry
  • Gene Expression Regulation
  • Hematopoiesis / immunology*
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cell Surface*
  • Receptors, Interleukin-2 / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells
  • Transcription Factors*

Substances

  • Membrane Glycoproteins
  • Membrane Proteins
  • NOTCH1 protein, human
  • Notch1 protein, mouse
  • RNA, Messenger
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Transcription Factors
  • pre-T cell receptor alpha