Buckley A F, Kuo C T, Leiden J M
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Nat Immunol. 2001 Aug;2(8):698-704. doi: 10.1038/90633.
T lymphocytes circulate in a quiescent state until they encounter cognate antigen bound to the surface of an antigen-presenting cell. The molecular pathways that regulate T cell quiescence remain largely unknown. Here we show that forced expression of the lung Krüppel-like transcription factor (LKLF) in Jurkat T cells is sufficient to program a quiescent phenotype characterized by decreased proliferation, reduced cell size and protein synthesis and decreased surface expression of activation markers. Conversely, LKLF-deficient peripheral T cells produced by gene targeting showed increased proliferation, increased cell size and enhanced expression of surface activation markers in vivo. LKLF appeared to function, at least in part, by decreasing expression of the proto-oncogene encoding c-Myc. Forced expression of LKLF was associated with markedly decreased c-Myc expression. In addition, many effects of LKLF expression were mimicked by expression of the dominant-negative MadMyc protein and rescued by overexpression of c-Myc. Thus, LKLF is both necessary and sufficient to program quiescence in T cells and functions, in part, by negatively regulating a c-Myc--dependent pathway.
T淋巴细胞以静止状态循环，直到它们遇到与抗原呈递细胞表面结合的同源抗原。调节T细胞静止的分子途径在很大程度上仍然未知。在此我们表明，在Jurkat T细胞中强制表达肺Krüppel样转录因子（LKLF）足以使细胞呈现静止表型，其特征为增殖减少、细胞大小和蛋白质合成降低以及活化标志物的表面表达减少。相反，通过基因靶向产生的LKLF缺陷外周T细胞在体内表现出增殖增加、细胞大小增大以及表面活化标志物表达增强。LKLF似乎至少部分通过降低编码c-Myc的原癌基因的表达发挥作用。LKLF的强制表达与c-Myc表达明显降低相关。此外，LKLF表达的许多效应可被显性负性MadMyc蛋白的表达模拟，并被c-Myc的过表达挽救。因此，LKLF对于T细胞静止的编程既是必需的也是充分的，并且部分通过负调节c-Myc依赖性途径发挥作用。
