Inducible expression of a p56Lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes.
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.
Legname
G
G
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
Seddon
B
B
Lovatt
M
M
Tomlinson
P
P
Sarner
N
N
Tolaini
M
M
Williams
K
K
Norton
T
T
Kioussis
D
D
Zamoyska
R
R
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
D015704:CD4 Antigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)