Chiao J W, Heil M, Arlin Z, Lutton J D, Choi Y S, Leung K
Proc Natl Acad Sci U S A. 1986 May;83(10):3432-6. doi: 10.1073/pnas.83.10.3432.
An inhibitor isolated from the serum-free culture medium of human myeloid leukemic HL-60 cells was able to suppress mitogen- and alloantigen-stimulated proliferative responses of normal lymphocytes in a dose-dependent manner. In vitro production, concentration, and purification by column chromatography and electrophoresis revealed that the inhibitor was produced constitutively, required RNA synthesis, and had a molecular weight in the range of 40,000-60,000. The inhibitor was also produced in vitro by myeloid leukemia cells isolated from patients with acute myelogenous leukemia. In a similar manner, the inhibitory material suppressed proliferative responses of allogeneic and autologous lymphocytes. Suppression was accompanied by drastically reduced production of interleukin 2 and lymphokines, which regulate differentiation of myeloid leukemia cells, and suppression was reversed by addition of exogenous interleukin 2. The inhibitor did not suppress clonogenic proliferation of normal granulocytes and macrophages suggesting that inhibition of production or interference with interleukin 2 activity as a possible mechanism. These interactions between leukemia cells and lymphocytes have shed new light on the immunosuppression and growth advantage of leukemia cells. Inhibitory activity of HL-60 cells was diminished after they were induced to differentiate, indicating that differentiation induced by lymphokines may be an effective means of controlling leukemia.
从人髓性白血病HL - 60细胞的无血清培养基中分离出的一种抑制剂，能够以剂量依赖的方式抑制正常淋巴细胞对丝裂原和同种异体抗原刺激的增殖反应。通过柱色谱和电泳进行体外生产、浓缩和纯化表明，该抑制剂是组成性产生的，需要RNA合成，分子量在40,000 - 60,000范围内。急性髓性白血病患者分离出的髓性白血病细胞在体外也能产生这种抑制剂。同样，这种抑制物质能抑制同种异体和自体淋巴细胞的增殖反应。抑制作用伴随着调节髓性白血病细胞分化的白细胞介素2和淋巴因子的产生大幅减少，并且通过添加外源性白细胞介素2可逆转这种抑制作用。该抑制剂不抑制正常粒细胞和巨噬细胞的克隆增殖，提示抑制白细胞介素2的产生或干扰其活性可能是一种作用机制。白血病细胞与淋巴细胞之间的这些相互作用为白血病细胞的免疫抑制和生长优势提供了新的线索。HL - 60细胞在被诱导分化后其抑制活性减弱，这表明淋巴因子诱导的分化可能是控制白血病的一种有效手段。
