Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment

Nat Immunol. 2001 Dec;2(12):1167-73. doi: 10.1038/ni733.


The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination. We found that these mice were unable to extinguish CD4 expression either in immature thymocytes or mature CD8+ cytotoxic T cells (CTLs), which resulted in the development of major histocompatibility complex class II-restricted double-positive CTLs in the periphery. This finding strongly supports a stochastic over an instructive mechanism of coreceptor down-regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / genetics*
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Lineage
  • Down-Regulation
  • Gene Silencing*
  • Gene Targeting
  • Histocompatibility Antigens Class II / physiology
  • Immunophenotyping
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Regulatory Sequences, Nucleic Acid
  • Response Elements
  • Sequence Deletion
  • Stochastic Processes
  • T-Lymphocyte Subsets / classification
  • T-Lymphocytes, Cytotoxic / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*


  • CD4 Antigens
  • Histocompatibility Antigens Class II