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β地中海贫血患儿异基因造血干细胞移植后辅助性T细胞17和调节性T细胞谱与移植物抗宿主病

T helper 17 and regulatory T-cell profile and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients with beta-thalassemia.

作者信息

Bayegi Shideh Namazi, Hamidieh Amir Ali, Behfar Maryam, Saghazadeh Amene, Bozorgmehr Mahmood, Karamlou Yalda, Shekarabi Mehdi, Tajik Nader, Delbandi Ali-Akbar, Zavareh Farzaneh Tofighi, Delavari Samaneh, Rezaei Nima

机构信息

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Pediatric Cell and Gene Therapy Research Center, Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Pediatric Cell and Gene Therapy Research Center, Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Transpl Immunol. 2023 Apr;77:101803. doi: 10.1016/j.trim.2023.101803. Epub 2023 Feb 24.


DOI:10.1016/j.trim.2023.101803
PMID:36842567
Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for hereditary hemoglobin disorders, such as beta-thalassemia; However, this procedure is not without constraints, mainly engendering complications such as acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), and susceptibility to infections. The clinical outcomes of allo-HSCT are highly dependant on the quality and quantity of T-cell subsets reconstitution. Following the allo-HSCT of six pediatric patients afflicted with beta-thalassemia, their mononuclear cells were isolated, and then cultured with a combination of phorbol myristate acetate (PMA)/ionomycin and Brefeldin A. The content of CD4 T-cell subsets, including T helper 17 (Th17) cells and regulatory T cells (Tregs), were determined by specific conjugated-monoclonal antibodies three and six months post-HSCT. An increased frequency of total CD4 T-cells, Tregs and Th17 cells was observed at day 90 and 180 after allo-HSCT, albeit the numbers were still lower than that of our healthy controls. In patients who developed cGvHD, a lower Th17/Treg ratio was observed, owing it to a decreased proportion of Th17 cells. In conclusion, creating balance between Th17 and Treg subsets may prevent acute and chronic GvHD in patients after allo-HSCT.

摘要

异基因造血干细胞移植(allo-HSCT)是治疗遗传性血红蛋白疾病(如β地中海贫血)的一种有效方法;然而,该 procedure 并非没有限制,主要会引发诸如急性移植物抗宿主病(aGvHD)、慢性移植物抗宿主病(cGvHD)以及感染易感性等并发症。allo-HSCT 的临床结果高度依赖于 T 细胞亚群重建的质量和数量。在对六名患有β地中海贫血的儿科患者进行 allo-HSCT 后,分离出他们的单核细胞,然后用佛波酯肉豆蔻酸酯乙酸酯(PMA)/离子霉素和布雷菲德菌素 A 的组合进行培养。在 HSCT 后三个月和六个月,通过特异性结合单克隆抗体测定 CD4 T 细胞亚群的含量,包括辅助性 T 细胞 17(Th17)细胞和调节性 T 细胞(Tregs)。在 allo-HSCT 后第 90 天和 180 天观察到总 CD4 T 细胞、Tregs 和 Th17 细胞的频率增加,尽管其数量仍低于健康对照组。在发生 cGvHD 的患者中,观察到 Th17/Treg 比值较低,这归因于 Th17 细胞比例的降低。总之,在 Th17 和 Treg 亚群之间建立平衡可能预防 allo-HSCT 后患者的急性和慢性 GvHD。

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