Abstract
The development and function of αβT lymphocytes depend on signals derived from pre-T and αβT cell receptors (preTCR and αβTCR) (reviewed in refs 1, 2). The engagement of these receptors leads to the activation of Lck and Fyn3,4, which are protein tyrosine kinases (PTKs) of the Src family. It remains unclear to what extent the activation of Src-family PTKs can direct the differentiation steps triggered by preTCR and αβTCR. Here we show that the inactivation of the negative regulator of Src-family PTKs, carboxy-terminal Src kinase (Csk)5, in immature thymocytes abrogates the requirement for preTCR, αβTCR and major histocompatibility complex (MHC) class II for the development of CD4+8+ double-positive and CD4+ single-positive thymocytes as well as peripheral CD4 αβT-lineage cells. These data show that Csk and its substrates are required to establish preTCR/αβTCR-mediated control over the development of αβT cells.
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Acknowledgements
We thank A. Berns and H. Jacobs for TCRβ−/− mice; H. Bluethmann and I. Förster for Aα−/− mice; D. Loh and M. Löhning for DO11.10 mice; C. Göttlinger, B. Meiners, S. Irlenbusch and C.Uthoff-Hachenberg for technical assistance; and J. Howard and K. Rajewsky for discussions and critical reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft through SFB 243. C.S. was supported by the Fonds der Chemie. K.S. was supported by an EMBO long-term fellowship.
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Schmedt, C., Saijo, K., Niidome, T. et al. Csk controls antigen receptor-mediated development and selection of T-lineage cells. Nature 394, 901–904 (1998). https://doi.org/10.1038/29802
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DOI: https://doi.org/10.1038/29802
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