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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.

Original publication

DOI

10.1002/(SICI)1521-4141(199908)29:08<2376::AID-IMMU2376>3.0.CO;2-7

Type

Journal article

Journal

Eur J Immunol

Publication Date

08/1999

Volume

29

Pages

2376 - 2384

Keywords

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