Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation

J Immunol. 1994 May 15;152(10):4783-92.


TCR-beta gene rearrangement or expression is necessary and sufficient for the progression of early alpha beta thymocyte differentiation from the CD3-CD4-CD8- triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR-beta rearrangement is currently thought to occur gradually. Some thymocytes were reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other thymocytes did not initiate TCR-beta rearrangement until the latest (CD44-CD25-) TN stage. Here, we have isolated subsets of TN thymocytes on the basis of surface expression of CD44 and CD25, with c-kit as an additional marker. We present a revised model of early T cell development in which TCR-beta and TCR-gamma rearrangements occur abruptly, at the CD44lowCD25+ c-kitlowTN stage. A high level of c-kit expression defines pro-T cells which have not yet rearranged their TCR genes. Germ-line TCR-beta transcripts, and transcripts of recombination activating genes (RAG)-1 and 2, are detected before TCR-beta gene rearrangement. Analyses of TN thymocytes of RAG-1 mutant mice, and of various TCR mutant and TCR transgenic RAG-1 mutant mice, indicate the existence of a control point at the CD44-CD25+TN stage at which cells expressing a productively rearranged TCR-beta chain are selected for further differentiation.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • CD3 Complex / analysis
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Carrier Proteins / analysis
  • DNA-Binding Proteins*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Homeodomain Proteins*
  • Hyaluronan Receptors
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Proteins / analysis
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Receptors, Cell Surface / analysis
  • Receptors, Colony-Stimulating Factor / analysis
  • Receptors, Lymphocyte Homing / analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*


  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Carrier Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • Proteins
  • Proto-Oncogene Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Cell Surface
  • Receptors, Colony-Stimulating Factor
  • Receptors, Lymphocyte Homing
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases