Inducible expression of a p56(Lck) transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes

The T lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is an esse ntial component of the TCR-mediated signal transduction complex. Lck knocko ut mice have reduced numbers of double-positive thymocytes and very few mat ure single-positive cells, particularly of the CD4 lineage. Here we demonst rate the ability of a tetracycline-based tissue-specific inducible Lck tran sgene to restore expansion of early thymocytes and maturation of single-pos itive cells in Lck(neg) mice upon induction with doxycycline. Restoration o f Lck expression is particularly important for positive selection to the CD 4(+) lineage but has a lesser impact on selection to the CD8(+) lineage, su ggesting activation of Lck is an important component of the signals involve d in lineage choice during thymic differentiation.