The T lymphocyte-specific protein tyrosine kinase p56lck (Lck) is an essential component of the TCR-mediated signal transduction complex. Lck knockout mice have reduced numbers of double-positive thymocytes and very few mature single-positive cells, particularly of the CD4 lineage. Here we demonstrate the ability of a tetracycline-based tissue-specific inducible Lck transgene to restore expansion of early thymocytes and maturation of single-positive cells in Lckneg mice upon induction with doxycycline. Restoration of Lck expression is particularly important for positive selection to the CD4+ lineage but has a lesser impact on selection to the CD8+ lineage, suggesting activation of Lck is an important component of the signals involved in lineage choice during thymic differentiation.

Inducible expression of a p56Lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes / Legname, Giuseppe; Seddon, B; Lovatt, M; Tomlinson, P; Sarner, N; Tolaini, M; Williams, K; Norton, T; Kioussis, D; Zamoyska, R.. - In: IMMUNITY. - ISSN 1074-7613. - 12:5(2000), pp. 537-546. [10.1016/S1074-7613(00)80205-8]

Inducible expression of a p56Lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes

Legname, Giuseppe;
2000-01-01

Abstract

The T lymphocyte-specific protein tyrosine kinase p56lck (Lck) is an essential component of the TCR-mediated signal transduction complex. Lck knockout mice have reduced numbers of double-positive thymocytes and very few mature single-positive cells, particularly of the CD4 lineage. Here we demonstrate the ability of a tetracycline-based tissue-specific inducible Lck transgene to restore expansion of early thymocytes and maturation of single-positive cells in Lckneg mice upon induction with doxycycline. Restoration of Lck expression is particularly important for positive selection to the CD4+ lineage but has a lesser impact on selection to the CD8+ lineage, suggesting activation of Lck is an important component of the signals involved in lineage choice during thymic differentiation.
2000
12
5
537
546
https://doi.org/10.1016/S1074-7613(00)80205-8
Legname, Giuseppe; Seddon, B; Lovatt, M; Tomlinson, P; Sarner, N; Tolaini, M; Williams, K; Norton, T; Kioussis, D; Zamoyska, R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/11982
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