The CD45 tyrosine phosphatase regulates CD3‐induced signal transduction and T cell development in recombinase‐deficient mice: restoration of pre‐TCR function …

S Pingel, M Baker, M Turner, N Holmes… - European journal of …, 1999 - Wiley Online Library
S Pingel, M Baker, M Turner, N Holmes, DR Alexander
European journal of immunology, 1999Wiley Online Library
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 …
Abstract
The pre‐TCR complex regulates the transition from CD4CD8 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 p56lck is critical for pre‐TCR signal transduction.
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