Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
Transplantation. 2012 Jun 27;93(12):1270-5. doi: 10.1097/TP.0b013e31824fd8b4.
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.
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 HLADRLin subset and antibodies against slanDCs, blood DC antigen 1 (CD1c mDCs), and blood DC antigen 2 (pDCs).
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.
These results indicate that SCT-associated complications such as bacterial infection, CMV reactivation, and acute GvHD can significantly modulate the frequency of slanDCs.
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(DCs)具有诱导先天和适应性免疫反应的非凡能力。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-硫酸神经氨酸 LacNAc 树突状细胞(slanDCs)是人类血液树突状细胞的主要亚群,具有高促炎能力。我们首次研究了 SCT 后患者血液中 slanDCs 的重建情况,并研究了细菌感染、巨细胞病毒(CMV)再激活和急性 GvHD 对其频率的调节作用。
80 例 SCT 后患者的外周血通过流式细胞术定量检测 slanDCs、CD1c 髓样树突状细胞(mDCs)和浆细胞样树突状细胞(pDCs)的频率。为了评估个体 DC 亚群,我们使用 HLADRLin 亚群的预门控和针对 slanDCs、血液树突状细胞抗原 1(CD1c mDCs)和血液树突状细胞抗原 2(pDCs)的抗体。
与 CD1c mDCs 和 pDCs 相比,slanDCs 在 SCT 后第一个月的重建速度最慢。有趣的是,在 SCT 后第二和第三个月,它们的百分比稳步增加,slanDCs 是最丰富的 DC 亚群。此外,我们观察到细菌感染、CMV 再激活或严重急性 GvHD 患者血液中 slanDCs 的频率明显降低。此外,slanDCs 在急性 GvHD 的类固醇治疗后显示出最显著的减少。
这些结果表明,与 SCT 相关的并发症,如细菌感染、CMV 再激活和急性 GvHD,可显著调节 slanDCs 的频率。