Choudhury A, Gajewski J L, Liang J C, Popat U, Claxton D F, Kliche K O, Andreeff M, Champlin R E
Department of Hematology and Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Blood. 1997 Feb 15;89(4):1133-42.
The success of adoptive immunotherapy for the treatment of leukemia depends on the generation of T cells that can specifically react with malignant cells. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we generated DCs from peripheral blood cells of patients with chronic myelogenous leukemia (CML). CML cells incubated concurrently with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha in vitro developed morphologic and phenotypic characteristics of DCs. Fluorescence in situ hybridization showed the presence of t(9;22) in the nuclei of these cells, indicating that they were leukemic in origin. These cells were potent stimulators of lymphocyte proliferation in specific in vitro assays for DC function. Autologous T cells stimulated with in vitro-generated, leukemic DCs displayed vigorous cytotoxic activity against CML cells but low reactivity to major histocompatability complex-matched normal bone marrow cells. Cytotoxic activity against CML targets was fourfold to sixfold higher using DC-stimulated autologous T cells than with autologous T cells expanded by culture with interleukin-2 alone. DC-stimulated T cells also inhibited growth of CML clonogenic precursors in colony-forming assays in vitro. These results suggest that cytokine-driven in vitro differentiation of CML cells results in generation of DCs with potent T-cell stimulatory function. In vitro-generated DCs can be effectively used as antigen-presenting cells for the ex vivo expansion of antileukemic T cells.
过继性免疫疗法治疗白血病的成功取决于能与恶性细胞特异性反应的T细胞的产生。树突状细胞（DCs）是抗白血病T细胞反应发展过程中重要的抗原呈递细胞。在本研究中，我们从慢性粒细胞白血病（CML）患者的外周血细胞中生成了DCs。在体外将CML细胞与粒细胞-巨噬细胞集落刺激因子、白细胞介素-4和肿瘤坏死因子-α共同孵育，这些细胞呈现出DCs的形态学和表型特征。荧光原位杂交显示这些细胞的细胞核中存在t(9;22)，表明它们起源于白血病细胞。在特定的DC功能体外检测中，这些细胞是淋巴细胞增殖的强效刺激剂。用体外生成的白血病DCs刺激自体T细胞，对CML细胞显示出强烈的细胞毒活性，但对主要组织相容性复合体匹配的正常骨髓细胞反应性较低。与仅用白细胞介素-2培养扩增的自体T细胞相比，用DC刺激的自体T细胞对CML靶标的细胞毒活性高4至6倍。在体外集落形成试验中，DC刺激的T细胞也抑制了CML克隆形成前体细胞的生长。这些结果表明，细胞因子驱动的CML细胞体外分化导致产生具有强效T细胞刺激功能的DCs。体外生成的DCs可有效地用作抗原呈递细胞，用于体外扩增抗白血病T细胞。
