Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts
Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts
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DOI：
10.1093/intimm/dxh139
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发表时间：
2004-10-01
影响因子：
4.4
通讯作者：
Wetzler, M
中科院分区：
文献类型：
--
作者：
Lee, J;Sait, SN;Wetzler, M
我们在此询问功能性树突状细胞是否可以从t（9;22）急性淋巴细胞白血病（ALL）母细胞中产生。我们首先确定白细胞介素(IL)-1 β、IL-3、IL-7、肿瘤坏死因子- α、干细胞因子和CD40配体的组合最适合从t(9;22) ALL细胞系中生成树突样细胞。培养6天后，5个细胞系中的4个表现出树突样形态，CCR7、CD54、CD80和CD86上调，细胞外蛋白摄取和T细胞活化，3例ALL患者的胚细胞也获得了类似的结果（9;22）。树突状细胞似乎由类似于未成熟和成熟树突状细胞（dc）的群体组成，通过CD80表达来区分。CD80-CD86+细胞被归类为未成熟dc，表现出高内吞能力，诱导的同种异体T细胞增殖最小，而CD80+CD86+细胞被归类为成熟dc，表现出可忽略的内吞能力，诱导的同种异体T细胞增殖强烈。这些成熟的树突样细胞诱导了自体细胞毒性T细胞对未修饰的原细胞的反应。综上所述，由t(9;22) ALL母细胞产生的CD80+CD86+细胞可用于t(9;22) ALL的过继免疫治疗。
We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cells from t(9;22) ALL cell lines. Following 6 days in culture, four of five cell lines demonstrated dendrite-like morphology, upregulation of CCR7, CD54, CD80 and CD86, uptake of extracellular proteins and activation of T cells, and similar results were obtained with blasts from three t(9;22) ALL patients. The dendritic-like cells appeared to be composed of populations resembling both immature and mature dendritic cells (DCs), distinguished by CD80 expression. CD80-CD86+ cells were classified as immature DCs, demonstrating high endocytic capability and inducing minimal allogeneic T cell proliferation, while CD80+CD86+ cells were classified as mature DCs, exhibiting negligible endocytic capability and inducing robust allogeneic T cell proliferation. These mature dendritic-like cells induced autologous cytotoxic T cell responses against the unmodified blasts in a patient who achieved prolonged remission. In summary, CD80+CD86+ cells generated from t(9;22) ALL blasts may be useful in adoptive immunotherapy for t(9;22) ALL.