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

Author(s): M. Tolaini, Thomas T. Norton, D Kioussis, S Avram, Giuseppe Legname, Ian P. Tomlinson, B Seddon, N Sarner, R Zamoyska, M Lovatt

Publication date: 2000-04-30

Journal: Immunity

Keywords: Animals, Antigens, CD4, CD4-Positive T-Lymphocytes, immunology, Cell Differentiation, Cell Lineage, Gene Expression Regulation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), genetics, Mice, Mice, Knockout, Mice, Transgenic

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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.