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异基因造血干细胞移植后供体来源的功能活性6-磺基乳糖胺阳性树突状细胞(slanDCs)的快速重建。

Rapid reconstitution of functionally active 6-sulfoLacNAc(+) dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant.

作者信息

Mimiola E, Marini O, Perbellini O, Micheletti A, Vermi W, Lonardi S, Costantini C, Meneghelli E, Andreini A, Bonetto C, Vassanelli A, Cantini M, Zoratti E, Massi D, Zamo' A, Leso A, Quaresmini G, Benedetti F, Pizzolo G, Cassatella M A, Tecchio C

机构信息

Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.

出版信息

Clin Exp Immunol. 2014 Oct;178(1):129-41. doi: 10.1111/cei.12387.

Abstract

The role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.

摘要

树突状细胞(DCs)和巨噬细胞在异基因造血干细胞移植(HSCT)中对于决定移植物抗宿主反应的程度至关重要。本研究的目的是分析造血干细胞(HSC)来源中的人类促炎性DCs亚群——皮肤淋巴细胞相关抗原阳性树突状细胞(slanDCs),并评估其在接受HSCT患者的外周血(PB)和骨髓(BM)中的1年重建动力学、起源和功能能力,以及它们在移植物抗宿主病(GVHD)组织标本中的存在情况。在整个重建过程中,还将HSC来源以及患者PB和BM中的slanDCs与髓样(m)DCs、浆细胞样(p)DCs和单核细胞进行了比较。slanDCs存在于所有HSC来源中。在患者的PB和BM中,从第+21天开始可识别出slanDCs,其频率中位数与健康供体相当,供体来源以及恢复动力学与mDCs、pDCs和单核细胞相似。在环孢素治疗下,slanDCs表现出正常的成熟模式,并在脂多糖(LPS)刺激后保持有效的趋化活性和释放肿瘤坏死因子(TNF)-α的能力。尽管如此,它们在GVHD组织标本中几乎检测不到,仅存在于肠道急性GVHD样本中。slanDCs早期重建,来源于供体且功能正常。大多数GVHD靶向组织标本中缺乏slanDCs,这似乎排除了这些细胞直接参与GVHD特征性的大多数局部反应的可能性。

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