University of Munich, Department for Haematopoietic Transplantations, Munich, Germany.
Cell Immunol. 2010;265(1):23-30. doi: 10.1016/j.cellimm.2010.06.009. Epub 2010 Jun 20.
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.
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。