The CD45 tyrosine phosphatase regulates CD3-induced signal transduction and T cell development in recombinase-deficient mice: restoration of pre-TCR function by active p56(lck)

Eur J Immunol. 1999 Aug;29(8):2376-84. doi: 10.1002/(SICI)1521-4141(199908)29:08<2376::AID-IMMU2376>3.0.CO;2-7.

Abstract

The pre-TCR complex regulates the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP) thymocytes during T cell development. In CD45(-/-) mice there is an accumulation of DN cells, suggesting a possible role for CD45 in pre-TCR signaling. We therefore crossed CD45(-/-) with Rag-1(-/-) mice to investigate the signaling functions of the CD3 complex in DN thymocytes. Remarkably, treatment of Rag-1(-/-)/CD45(-/-) mice with a CD3 mAb caused maturation to the DP stage at only 3% of the level measured in Rag-1(-/-) mice. Furthermore, ligation of the CD3 complex on Rag-1(-/-) /CD45(-/-) thymocytes in vitro induced less tyrosine phosphorylation in specific proteins when compared to Rag-1(-/-) thymocytes. CD45(-/-) mice were also crossed with pLGFA mice expressing a constitutively active form of the lck tyrosine kinase which restored the DN to DP transition to near normal levels. Our results are consistent with a model in which CD45-activated p56(lck) is critical for pre-TCR signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / metabolism*
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Differentiation
  • DNA Nucleotidyltransferases / deficiency*
  • DNA Nucleotidyltransferases / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Integrases*
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinases
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tyrosine / metabolism

Substances

  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell
  • Recombinases
  • RAG-1 protein
  • Tyrosine
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • DNA Nucleotidyltransferases
  • Integrases
  • integron integrase IntI1
  • Leukocyte Common Antigens