Another view of the selective model of thymocyte selection

Cell. 1993 Apr 23;73(2):225-36. doi: 10.1016/0092-8674(93)90225-f.


Thymocyte commitment to the CD4 helper versus CD8 cytotoxic lineage has not been satisfactorily established. Two models have been elaborated: one based on instruction, the other on selection. Most previous results support the instructive model, but our comparison of thymocyte differentiation in MHC class II-, class I- and double-deficient mice provides data challenging it. There exists a significant population of CD4 single positive cells in class II-deficient animals that is intermediate in maturity between CD4+CD8+ and end-stage CD4+CD8- thymocytes and is selected on class I molecules; an equivalent CD8+CD4- population occurs in class I-deficient animals. We propose a selective model entailing two TCR-MHC molecule engagements: the first provokes random down-modulation of either CD4 or CD8 and a degree of differentiation; the second, requiring participation of the appropriate coreceptor, permits end-stage differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Base Sequence
  • Bromodeoxyuridine / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD8 Antigens / analysis
  • Cell Differentiation
  • Cell Division
  • DNA / biosynthesis
  • DNA Nucleotidylexotransferase / metabolism
  • Flow Cytometry
  • Histocompatibility Antigens Class I / physiology
  • Histocompatibility Antigens Class II / genetics*
  • Homeodomain Proteins*
  • Ionomycin / pharmacology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Proteins / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Helper-Inducer / cytology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymus Gland / cytology*
  • Thymus Gland / embryology


  • Antigens, Differentiation, T-Lymphocyte
  • CD8 Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Homeodomain Proteins
  • Oligodeoxyribonucleotides
  • Proteins
  • Receptors, Antigen, T-Cell
  • RAG-1 protein
  • Ionomycin
  • DNA
  • DNA Nucleotidylexotransferase
  • Bromodeoxyuridine
  • Tetradecanoylphorbol Acetate