Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan.
Life Sci. 2011 Dec 19;89(25-26):946-55. doi: 10.1016/j.lfs.2011.10.005. Epub 2011 Oct 20.
Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological disorders, there is persistent immunosuppression in both allogeneic and autologous HSCT. Dendritic cells (DCs) play key roles in the immune system. This study investigated whether the DC progenitor cells within patients' peripheral blood after HSCT have the potential to differentiate into DCs.
Twenty-eight patients were included in this study, and peripheral blood samples were basically taken before starting the conditioning regimen, on the day of transplantation (day 0), and on days +14, +28, +42, +70 and +170 after transplantation. Immature DCs (iDCs) were induced from adherent mononuclear cells by using recombinant human granulocyte-macrophage colony-stimulating factor plus interleukin-4.
The iDCs expressed cell surface antigens such as CD40 and HLA-DR, and they had phagocytotic activity, thus showing the characteristics of iDCs. The induction of iDCs was possible from day +14 after HSCT. However, there were differences between allogeneic and autologous HSCT in the expression of CCR5 in iDCs at day +14 after transplantation. Furthermore, the up-regulation of maturation-related antigens by maturation stimuli was higher after HSCT compared with before HSCT.
We demonstrated that patients' peripheral blood mononuclear cells have the potential to differentiate into DCs beginning on day +14 after HSCT, although some differences exist between allogeneic and autologous HSCT and between before and after HSCT.
尽管造血干细胞移植(HSCT)是许多血液系统疾病的一种根治性治疗方法,但异体和自体 HSCT 后仍存在持续的免疫抑制。树突状细胞(DC)在免疫系统中发挥关键作用。本研究旨在探讨 HSCT 后患者外周血中的 DC 前体细胞是否具有分化为 DC 的潜力。
本研究纳入 28 例患者,基本在开始预处理方案前、移植日(第 0 天)以及移植后第 14、28、42、70 和 170 天采集外周血样本。使用重组人粒细胞-巨噬细胞集落刺激因子联合白细胞介素-4 从贴壁单核细胞中诱导未成熟 DC(iDC)。
iDC 表达 CD40 和 HLA-DR 等细胞表面抗原,具有吞噬活性,表现出 iDC 的特征。HSCT 后第 14 天即可诱导 iDC 生成。然而,异体和自体 HSCT 之间以及 HSCT 前后在移植后第 14 天 iDC 中 CCR5 的表达存在差异。此外,与 HSCT 前相比,成熟刺激物对成熟相关抗原的上调作用更高。
我们证实,尽管异体和自体 HSCT 之间以及 HSCT 前后存在差异,但 HSCT 后患者外周血单个核细胞具有分化为 DC 的潜力,第 14 天即可开始。