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Publication : 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).

First Author  Pingel S Year  1999
Journal  Eur J Immunol Volume  29
Issue  8 Pages  2376-84
PubMed ID  10458749 Mgi Jnum  J:56776
Mgi Id  MGI:1342406 Doi  10.1002/(SICI)1521-4141(199908)29:08<2376::AID-IMMU2376>3.0.CO;2-7
Citation  Pingel S, et al. (1999) 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 29(8):2376-84
abstractText  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.
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