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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
Author(s) -
Pingel Sabine,
Baker Matthew,
Turner Martin,
Holmes Nick,
Alexander Denis R.
Publication year - 1999
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/(sici)1521-4141(199908)29:08<2376::aid-immu2376>3.0.co;2-7
Subject(s) - t cell receptor , biology , cd3 , double negative , thymocyte , signal transduction , cd8 , protein tyrosine phosphatase , t cell , tyrosine phosphorylation , phosphorylation , microbiology and biotechnology , tyrosine kinase , immunology , antigen , immune system
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.