Greene W C, Robb R J, Depper J M, Leonard W J, Drogula C, Svetlik P B, Wong-Staal F, Gallo R C, Waldmann T A
J Immunol. 1984 Aug;133(2):1042-7.
In general, the human acute T lymphocytic leukemias are composed of malignant expansions of immature T cells lacking membrane receptors for T cell growth factor (TCGF, interleukin 2) and significant immunoregulatory activity. We investigated whether cultured acute lymphocytic leukemic T cell lines can be induced to differentiate and express the Tac antigen, a cell surface protein that contains a TCGF-binding site, after exposure to phorbol 12-myristate 13-acetate (PMA) and/or phytohemagglutinin (PHA). Reactivity of anti-Tac with induced leukemic T cells was studied by three techniques, including: 1) flow microfluorometry; 2) specific binding of [3H]anti-Tac; and 3) receptor immunoprecipitation with anti-Tac and analysis by SDS-PAGE. After exposure to PMA with or without PHA, both JURKAT and HSB-2 acute lymphocytic leukemic T cells displayed Tac antigen within 6 to 8 hr. Induction of receptor expression was blocked by actinomycin D, suggesting a requirement for new mRNA transcription. Induced JURKAT cells contained approximately 7000 Tac molecules per cell, and the binding of anti-Tac to these cells was blocked in a dose-related manner by purified TCGF but not by insulin or purified recombinant interferon-alpha. SDS-PAGE analysis of anti-Tac immunoprecipitates demonstrated that receptors present on induced JURKAT cells were 2000 to 3000 daltons smaller than those present on PHA-activated normal lymphoblasts or induced HSB-2 cells. Induction of JURKAT cells with both PHA and PMA resulted in marked secretion of TCGF as well as the appearance of Tac antigen. After activation of these cells with PMA alone, Tac antigen was similarly expressed, but the level of TCGF synthesis was less than 1% of that obtained after dual induction with PHA and PMA. These data indicate that the signals required for TCGF synthesis and Tac expression are not identical, and furthermore that induction of Tac antigen and TCGF is not obligately linked in these cells.
一般来说，人类急性T淋巴细胞白血病是由缺乏T细胞生长因子（TCGF，白细胞介素2）膜受体且免疫调节活性显著的未成熟T细胞恶性增殖组成。我们研究了培养的急性淋巴细胞白血病T细胞系在暴露于佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）和/或植物血凝素（PHA）后是否能被诱导分化并表达Tac抗原，Tac抗原是一种含有TCGF结合位点的细胞表面蛋白。通过三种技术研究了抗Tac与诱导的白血病T细胞的反应性，包括：1）流式微荧光测定法；2）[3H]抗Tac的特异性结合；3）用抗Tac进行受体免疫沉淀并用SDS - PAGE分析。在暴露于含或不含PHA的PMA后，JURKAT和HSB - 2急性淋巴细胞白血病T细胞在6至8小时内均显示出Tac抗原。放线菌素D可阻断受体表达的诱导，这表明需要新的mRNA转录。诱导的JURKAT细胞每个细胞含有约7000个Tac分子，纯化的TCGF可按剂量相关方式阻断抗Tac与这些细胞的结合，而胰岛素或纯化的重组干扰素 - α则不能。对抗Tac免疫沉淀物的SDS - PAGE分析表明，诱导的JURKAT细胞上存在的受体比PHA激活的正常淋巴母细胞或诱导的HSB - 2细胞上存在的受体小2000至3000道尔顿。用PHA和PMA同时诱导JURKAT细胞导致TCGF的显著分泌以及Tac抗原的出现。仅用PMA激活这些细胞后，Tac抗原也同样表达，但TCGF合成水平低于PHA和PMA双重诱导后获得水平的1%。这些数据表明，TCGF合成和Tac表达所需的信号并不相同，此外，在这些细胞中Tac抗原的诱导和TCGF的诱导并非必然相关。
