title: Inducible expression of a p56Lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes.
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.
authors.affiliation: Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Legname
authors.forename: B
authors.initials: B
authors.lastname: Seddon
authors.forename: M
authors.initials: M
authors.lastname: Lovatt
authors.forename: P
authors.initials: P
authors.lastname: Tomlinson
authors.forename: N
authors.initials: N
authors.lastname: Sarner
authors.forename: M
authors.initials: M
authors.lastname: Tolaini
authors.forename: K
authors.initials: K
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Norton
authors.forename: D
authors.initials: D
authors.lastname: Kioussis
authors.forename: R
authors.initials: R
authors.lastname: Zamoyska
mesh_terms: D000818:Animals; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D015704:CD4 Antigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)