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刺激来自急性髓细胞白血病(AML)或骨髓增生异常综合征(MDS)患者的白血病衍生树突状细胞(DC)后 T 细胞的质量可预测其对白血病的细胞毒性潜力。

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.

机构信息

University of Munich, Department for Haematopoietic Transplantations, Munich, Germany.

出版信息

Cell Immunol. 2010;265(1):23-30. doi: 10.1016/j.cellimm.2010.06.009. Epub 2010 Jun 20.

Abstract

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.

摘要

髓系白血病细胞可分化为白血病衍生树突状细胞 (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。为了进一步研究 DC/DC(leu)诱导的 T 细胞反应模式,我们在匹配(同种异体)供体 T 细胞(n=6)、干细胞移植后复发时制备的 T 细胞(n=4)或(自体)患者 T 细胞(n=7)的混合淋巴细胞培养(MLC)前后进行了(功能)流式细胞术/荧光溶解测定,与含 blast 的单核细胞 ('MNC') 或含 DC(leu)的 DC ('DC')。与 'MNC' 相比,'DC' 是更好的抗白血病 T 细胞活性的介质,尽管并非在所有情况下都有效。我们可以在 'MNC' 或 'DC' 刺激后定义成熟 DC、DC(leu)、增殖、CD4(+)、CD8(+)和非幼稚 T 细胞的比例截断值,这些值可预测刺激 T 细胞的抗白血病活性以及对免疫治疗的反应。有趣的是,尤其是在 DC 刺激后,CD4:CD8 或 CD45RO:CD45RA T 细胞的比值>1 可预测抗白血病功能。总之,MLC 刺激阶段后 DC 和 T 细胞的组成和质量可预测体外和体内抗白血病反应的成功,特别是与增殖、CD4(+) 和 CD45RO(+) T 细胞的比例有关。成功的细胞毒性和 'DC' 刺激后 T 细胞记忆的发展可预测疾病的临床过程,并可能为开发过继免疫疗法铺平道路,特别是对于 SCT 后复发的患者。

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