Legname G, Seddon B, Lovatt M, Tomlinson P, Sarner N, Tolaini M, Williams K, Norton T, Kioussis D, Zamoyska R
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
Immunity. 2000 May;12(5):537-46. doi: 10.1016/s1074-7613(00)80205-8.
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.
T淋巴细胞特异性蛋白酪氨酸激酶p56lck（Lck）是TCR介导的信号转导复合物的重要组成部分。Lck基因敲除小鼠的双阳性胸腺细胞数量减少，成熟的单阳性细胞很少，尤其是CD4谱系的细胞。在此，我们证明了基于四环素的组织特异性可诱导Lck转基因在强力霉素诱导后能够恢复Lck基因敲除小鼠早期胸腺细胞的增殖和单阳性细胞的成熟。Lck表达的恢复对CD4+谱系的阳性选择尤为重要，但对CD8+谱系的选择影响较小，这表明Lck的激活是胸腺分化过程中谱系选择所涉及信号的重要组成部分。
