慢性粒细胞性白血病细胞诱导分化的树突状细胞及其抗原提呈作用的研究

Study on the cytotoxic activity of the leukemic dendritic cells stimulated by T cells in vitro

观察细胞因子联合培养诱生的慢性粒细胞性白血病(CML)细胞白血病性树突状细胞(DC)的细胞特性及抗原提呈作用。选择CML患者的骨髓细胞和CML性细胞株K562细胞,应用GM-CSF+IL-4+TNF-α联合培养后进行细胞表型和特异性激活淋巴细胞作用的检测。CML-DC和K562-DC具有DC的形态特征和超微结构,表达CD1a、CD80和CD86等DC相关抗原,并可激活淋巴细胞产生增殖反应,并产生针对白血病细胞的特异性细胞毒效应,同时DC可不同程度地分泌IL-12并协助淋巴细胞产生IFN-γ。CML患者的细胞和K562细胞在细胞因子的诱导下,可分化为具有DC表型特性和特异性激活T细胞的白血病性抗原提呈细胞,使白血病DC瘤苗的应用成为可能。

To investigate the phenotypes and functions of dendritic cells cocuhivated with cytokines from peripheral blood monocytes of patients with chronic myelogenous leukemia （CML） and K562 cells in vitro, PBMN of patients with CML and K562 cells that incubated concurrently with GM-CSF, IL-4 and TNF-α for 14 days were cocultivated to induce the generation of the leukemic dendritic cells （L-DC）, and then the phenotypes of cells and the specific action to stimulate T lymphocytes were determined by FACS analysis and their antigen presentation function by cytotoxity determinations. It was found that the L-DC（CML-DC and K562-DC） were demonstrated to have the characteristic morphology and ultra-structures of dendritic cells, expressing the DC-associated antigens, such as CD1a, CD80 and CD86. In addition, they could activate lymphocytes to proliferate and produce the specific cytotoxity effect against leukemic cells. Meanwhile, they could secrete cytokine IL-12 and induce lymphocytes to secrete IFN-γ It is concluded that cells from CML patients and K562 cells can differentiate into leukemic antigen-presenting ceils with characteristic phenotype of dendritic cells and the capacity to activate T ceils specifically, rendering the possibility of application of DC vaccine for the treatment of patients with leukemia to be evident.