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首页> 外文期刊>Cellular immunology >Quality of T-cells after stimulation with leukemia-derived dendritic cells (DC) from patients with acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) is predictive for their leukemia cytotoxic potential
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Quality of T-cells after stimulation with leukemia-derived dendritic cells (DC) from patients with acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) is predictive for their leukemia cytotoxic potential

机译：急性髓性白血病（AML）或髓样增生异常综合征（MDS）患者的白血病来源的树突状细胞（DC）刺激后，T细胞的质量可预测其白血病的细胞毒性潜力

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摘要

Myeloid leukemic cells can differentiate into leukemia-derived dendritic cells (DC leu), presenting known/unknown leukemic-antigens. Induced anti-leukemic T-cell-responses are variable. To further elicit DC/DC leu-induced T-cell-response-patterns we performed (functional)flow-cytometry/fluorolysis-assays before/after mixed lymphocyte cultures (MLC) of matched (allogeneic) donor-T-cells (n=6), T-cells prepared at relapse after stem cell transplantation (n=4) or (autologous) patients'-T-cells (n=7) with blast-containing-mononuclear-cells ('MNC') or DC leu-containing DC ('DC'). Compared to 'MNC' 'DC' were better mediators of anti-leukaemic T-cell-activity, although not in every case effective. We could define cut-off proportions of mature DC, DC leu, proliferating, CD4 +, CD8 + and non-naive T-cells after 'MNC'- or 'DC'-stimulation, that were predictive for an anti-leukemic-activity of stimulated T-cells as well as a response to immunotherapy. Interestingly especially ratios 1 of CD4:CD8 or CD45RO:CD45RA T-cells were predictive for anti-leukemic function after DC-stimulation.In summary the composition and quality of DC and T-cells after a MLC-stimulating-phase is predictive for a successful ex-vivo and in-vivo anti-leukemic response, especially with respect to proportions of proliferating, CD4 + and CD45RO + T-cells. Successful cytotoxicity and the development of a T-cell-memory after 'DC'-stimulation could be predictive for the clinical course of the disease and may pave the way to develop adoptive immunotherapy, especially for patients at relapse after SCT.
机译：髓样白血病细胞可以分化为白血病来源的树突状细胞（DC leu），呈递已知/未知的白血病抗原。诱导的抗白血病T细胞反应是可变的。为了进一步引出DC / DC leu诱导的T细胞反应模式，我们在匹配的（同种异体）供体T细胞的混合淋巴细胞培养（MLC）之前/之后进行了（功能性）流式细胞仪/荧光分析法（n = 6），干细胞移植后复发时准备的T细胞（n = 4）或（自体）患者的T细胞（n = 7）含有胚细胞含单核细胞（'MNC'）或DC leu-包含DC（'DC'）。与'MNC'相比，'DC'是抗白血病T细胞活性的更好的介质，尽管并非在每种情况下都有效。我们可以定义“ MNC”或“ DC”刺激后成熟DC，DC leu，增殖，CD4 +，CD8 +和非幼稚T细胞的截止比例，这些比例可预测抗白血病活性刺激的T细胞以及对免疫疗法的反应。有趣的是，尤其是CD4：CD8或CD45RO：CD45RA T细胞的比率> 1可以预测DC刺激后的抗白血病功能。总而言之，MLC刺激阶段后DC和T细胞的组成和质量可以预测成功的离体和体内抗白血病反应，尤其是在增殖性CD4 +和CD45RO + T细胞比例方面。成功的细胞毒性和“ DC”刺激后T细胞记忆的发展可能是疾病的临床过程的预兆，并可能为过继免疫疗法的发展铺平道路，特别是对于SCT后复发的患者。

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