Csk controls antigen receptor-mediated development and selection of T-lineage cells

Christian Schmedt (), Kaoru Saijo, Tetsuhiro Niidome, Ralf Kühn, Shinichi Aizawa and Alexander Tarakhovsky
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Christian Schmedt: Laboratory for Lymphocyte Signalling Department of Immunology
Kaoru Saijo: Laboratory for Lymphocyte Signalling Department of Immunology
Tetsuhiro Niidome: Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine
Ralf Kühn: Laboratory for Lymphocyte Signalling Institute for Genetics, University of Cologne
Shinichi Aizawa: Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine
Alexander Tarakhovsky: Laboratory for Lymphocyte Signalling Department of Immunology

Nature, 1998, vol. 394, issue 6696, 901-904

Abstract: 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.

Date: 1998
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DOI: 10.1038/29802

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