Arima N, Daitoku Y, Yamamoto Y, Fujimoto K, Ohgaki S, Kojima K, Fukumori J, Matsushita K, Tanaka H, Onoue K
J Immunol. 1987 May 1;138(9):3069-74.
To examine the possibility of heterogeneous mechanisms in the proliferation of adult T cell leukemia (ATL) cells, leukemic cells from 13 patients, nine acute-type and four chronic-type ATL, were examined for the production of interleukin 2 (IL 2) with or without mitogenic stimulation and their response to recombinant IL 2 when exogeneously added. The leukemic cells were classified into four groups, as follows. Group 1 (two patients): Cells of this group produced IL 2 messenger RNA, secreted IL 2, and proliferated when cultured in mitogen-free medium. The spontaneous proliferation of the cells in mitogen-free medium was inhibited by anti-Tac/IL 2 receptor and anti-IL 2 monoclonal antibodies. Moreover, the thymidine incorporation by the cells was enhanced in response to exogeneously added recombinant IL 2 and IL 2 produced by themselves. These results indicate that the ATL cells of this group proliferate with autostimulation by IL 2. Group 2 (seven patients): Cells of this group did not secrete IL 2 when cultured in mitogen-free medium, but the cells showed response to exogeneously added recombinant IL 2 and proliferated in culture. These results indicate that the ATL cells of this group proliferate by a paracrine mechanism. Group 3 (one patient): Cells of this group secreted IL 2 in mitogen-free medium. However, the spontaneous proliferation of these cells in vitro was very low, and the response to recombinant IL 2 was also very low. Group 4 (three patients): Cells of this group did not secrete IL 2 in mitogen-free medium. Spontaneous proliferation and the response to recombinant IL 2 were also very low. The clinical feature of all patients of Groups 1 and 2 was acute-type, and that of Groups 3 and 4 was chronic-type. Thus, we conclude that heterogeneous mechanisms exist in the proliferation of leukemic cells, and that growth rate in mitogen-free medium and response to IL 2 of the cells may have a significant relationship to the clinical feature, acute- or chronic-type.
为研究成人T细胞白血病（ATL）细胞增殖过程中存在异质性机制的可能性，我们检测了13例患者的白血病细胞，其中9例为急性型ATL，4例为慢性型ATL，观察有无丝裂原刺激时白细胞介素2（IL-2）的产生情况，以及外源性添加重组IL-2时它们对重组IL-2的反应。白血病细胞分为以下四组。第1组（2例患者）：该组细胞产生IL-2信使核糖核酸，分泌IL-2，且在无丝裂原培养基中培养时增殖。无丝裂原培养基中细胞的自发增殖受到抗Tac/IL-2受体单克隆抗体和抗IL-2单克隆抗体的抑制。此外，外源性添加重组IL-2以及细胞自身产生的IL-2均可增强细胞的胸腺嘧啶核苷掺入。这些结果表明，该组ATL细胞通过IL-2的自分泌刺激进行增殖。第2组（7例患者）：该组细胞在无丝裂原培养基中培养时不分泌IL-2，但细胞对外源性添加的重组IL-2有反应并在培养中增殖。这些结果表明，该组ATL细胞通过旁分泌机制增殖。第3组（1例患者）：该组细胞在无丝裂原培养基中分泌IL-2。然而，这些细胞在体外的自发增殖非常低，对重组IL-2的反应也非常低。第4组（3例患者）：该组细胞在无丝裂原培养基中不分泌IL-2。自发增殖以及对重组IL-2的反应也非常低。第1组和第2组所有患者的临床特征为急性型，第3组和第4组为慢性型。因此，我们得出结论，白血病细胞增殖过程中存在异质性机制，且细胞在无丝裂原培养基中的生长速率以及对IL-2的反应可能与急性或慢性型临床特征存在显著关系。
