Kuo C T, Veselits M L, Leiden J M
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Science. 1997 Sep 26;277(5334):1986-90. doi: 10.1126/science.277.5334.1986.
Mature single-positive (SP) T lymphocytes enter a "resting" state in which they are proliferatively quiescent and relatively resistant to apoptosis. The molecular mechanisms regulating this quiescent phenotype were unknown. Here it was found that the expression of a Kruppel-like zinc finger transcription factor, lung Kruppel-like factor (LKLF), is developmentally induced during the maturation of SP quiescent T cells and rapidly extinguished after SP T cell activation. LKLF-deficient T cells produced by gene targeting had a spontaneously activated phenotype and died in the spleen and lymph nodes from Fas ligand-induced apoptosis. Thus, LKLF is required to program the quiescent state of SP T cells and to maintain their viability in the peripheral lymphoid organs and blood.
成熟的单阳性(SP)T淋巴细胞进入一种“静止”状态,在此状态下它们增殖静止且相对抗凋亡。调节这种静止表型的分子机制尚不清楚。在此研究中发现,一种Kruppel样锌指转录因子——肺Kruppel样因子(LKLF)的表达,在SP静止T细胞成熟过程中受到发育诱导,而在SP T细胞活化后迅速消失。通过基因靶向产生的LKLF缺陷型T细胞具有自发活化表型,并在脾脏和淋巴结中因Fas配体诱导的凋亡而死亡。因此,LKLF是编程SP T细胞静止状态并维持其在外周淋巴器官和血液中生存能力所必需的。