Reconstitution of 6-Sulfo LacNAc Dendritic Cells After Allogeneic Stem-Cell Transplantation
Reconstitution of 6-Sulfo LacNAc Dendritic Cells After Allogeneic Stem-Cell Transplantation
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DOI：
10.1097/tp.0b013e31824fd8b4
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发表时间：
2012-06-27
期刊：
影响因子：
6.2
通讯作者：
Tuve, Sebastian
中科院分区：
文献类型：
--
作者：
Mager, Konrad;Wehner, Rebekka;Tuve, Sebastian
背景感染和急性移植物抗宿主病（GvHD）是异基因干细胞移植（SCT）的主要并发症。树突状细胞（Dendritic cells，DCs）具有诱导先天性和适应性免疫反应的能力。因此，它们在消除病原体和急性GvHD的发病机制中起着至关重要的作用。6-Sulfo LacNAc DC（slanDC）是具有高促炎能力的人血液DC的主要亚群。我们首次研究了SCT后患者血液中slanDCs的重建以及细菌感染、巨细胞病毒（CMV）再激活和急性GvHD对其频率的调节。采用流式细胞术检测80例SCT后患者外周血中slanDCs、CD 1c（+）髓样DCs（mDCs）和浆细胞样DCs（pDCs）的频率。为了评估单个DC亚群，我们使用了HLADR（+）Lin（-）亚群的预设门和针对slanDC、血液DC抗原1（CD 1c（+）mDC）和血液DC抗原2（pDC）的抗体。与CD 1c（+）mDC和pDC相比，SlanDC在SCT后第一个月表现出最慢的重建。有趣的是，在SCT后的第二和第三个月，它们的百分比稳步增加，并且slanDC是最丰富的DC亚群。此外，我们还观察到细菌感染、CMV再激活或严重急性GvHD患者血液中slanDC的频率显著降低。此外，slan DCs在急性GvHD的类固醇治疗后表现出最显著的减少。这些结果表明，SCT相关的并发症，如细菌感染，CMV再激活，和急性GvHD可以显着调节slanDC的频率。
Background. Infections and acute graft-versus-host disease (GvHD) represent major complications of allogeneic stem-cell transplantation (SCT). Dendritic cells (DCs) display an extraordinary capacity to induce innate and adaptive immune responses. Therefore, they play a crucial role in the elimination of pathogens and in the pathogenesis of acute GvHD. 6-Sulfo LacNAc DCs (slanDCs) are a major subpopulation of human blood DCs with a high proinflammatory capacity. We investigated for the first time the reconstitution of slanDCs in the blood of patients after SCT and the modulation of their frequency by bacterial infection, cytomegalovirus (CMV) reactivation, and acute GvHD.Methods. The frequency of slanDCs, CD1c(+) myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) in the peripheral blood was quantified by flow cytometry in 80 patients after SCT. To assess individual DC subsets, we used pregating of the HLADR(+)Lin(-) subset and antibodies against slanDCs, blood DC antigen 1 (CD1c(+) mDCs), and blood DC antigen 2 (pDCs).Results. SlanDCs showed the slowest reconstitution in the first month after SCT compared with CD1c(+) mDCs and pDCs. Interestingly, in the second and third months after SCT, their percentage steadily increased, and slanDCs were the most abundant DC subset. In addition, we observed a markedly reduced frequency of slanDCs in the blood of patients with bacterial infection, CMV reactivation, or severe acute GvHD. Furthermore, slanDCs showed the most prominent reduction after steroid treatment of acute GvHD.Conclusions. These results indicate that SCT-associated complications such as bacterial infection, CMV reactivation, and acute GvHD can significantly modulate the frequency of slanDCs.