Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cells

Immunity. 1999 Jul;11(1):91-101. doi: 10.1016/s1074-7613(00)80084-9.


Signaling through the pre-TCR is essential for early T cell development and is severely impaired in mice lacking the CD3 gamma chain of the pre-TCR. We here address the molecular mechanisms underlying this defect. Impaired pre-TCR signaling is shown to be associated with a profound increase in the number of apoptotic CD4- CD8- (DN) thymocytes. Introduction of p53 deficiency into CD3 gamma-deficient mice completely reverses the cell survival defect in CD3 gamma-deficient DN thymocytes and rescues the block in pre-T cell differentiation. In addition, the CD4+ CD8+ (DP) compartment is expanded to its normal size. These findings suggest that the pre-TCR regulates progression through the DNA-damage checkpoint of the DN to DP transition by inactivating p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • CD3 Complex / genetics
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Antigen, T-Cell / deficiency
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Thymus Gland / cytology
  • Thymus Gland / pathology
  • Transgenes / immunology
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics


  • CD3 Complex
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • Tumor Suppressor Protein p53