Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytes

Cell. 1993 Apr 23;73(2):237-47. doi: 10.1016/0092-8674(93)90226-g.


Thymocytes that coexpress the CD4 and CD8 glycoproteins differentiate into mature CD4+ helper or CD8+ cytotoxic cells depending on whether their antigen receptors are specific for MHC class II or class I molecules, respectively. The mechanism of this decision process was investigated in mice whose T cell development was biased toward the class II-specific lineage. We found that constitutive expression of CD4 allows a developmentally arrested population of thymocytes that have mismatched class II-specific TCRs and the CD8 coreceptor to be rescued and to acquire a cytotoxic phenotype. This result is consistent with a two-step process of thymocyte maturation, in which there is stochastic down-regulation of either CD4 or CD8 and subsequent selection based on the ability of the TCR and remaining coreceptor to engage the same MHC molecule.

Publication types

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

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • CD4-Positive T-Lymphocytes / cytology*
  • CD8 Antigens / physiology*
  • Cell Differentiation
  • Flow Cytometry
  • Histocompatibility Antigens Class I / physiology
  • Histocompatibility Antigens Class II / physiology
  • Lymph Nodes / cytology
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / physiology
  • Stochastic Processes
  • T-Lymphocyte Subsets / cytology*
  • Thymus Gland / cytology
  • beta 2-Microglobulin / deficiency


  • CD4 Antigens
  • CD8 Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell
  • beta 2-Microglobulin