Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia
Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia
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DOI：
10.1182/blood.v89.4.1133
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发表时间：
1997-02-15
期刊：
影响因子：
20.3
通讯作者：
Champlin, RE
中科院分区：
文献类型：
--
作者：
Choudhury, A;Gajewski, JL;Champlin, RE
白血病的过继性免疫疗法的成功取决于T细胞的产生，这些T细胞可以特异性地与恶性细胞发生反应。树突状细胞（dc）是抗白血病t细胞反应发展中重要的抗原呈递细胞。在这项研究中，我们从慢性髓性白血病（CML）患者的外周血细胞中生成DCs。体外培养的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同时培养，形成了dc的形态和表型特征。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。在DC功能的特异性体外实验中，这些细胞是淋巴细胞增殖的有效刺激物。体外生成的白血病dc刺激自体T细胞对CML细胞表现出强烈的细胞毒性活性，但对主要组织相容性复合物匹配的正常骨髓细胞的反应性较低。使用dc刺激的自体T细胞对CML靶点的细胞毒活性比单独用白细胞介素-2培养扩增的自体T细胞高4到6倍。在体外集落形成实验中，dc刺激的T细胞也抑制CML克隆性前体的生长。这些结果表明，细胞因子驱动的CML细胞体外分化导致具有强大t细胞刺激功能的dc的产生。体外生成的树突状细胞可以有效地作为抗原提呈细胞用于抗白血病T细胞的体外扩增。(C) 1997年由美国血液病学会出版。
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. (C) 1997 by The American Society of Hematology.