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儿童造血干细胞移植后 FOXP3+ T 细胞的干细胞来源依赖性重建及其与同种异体反应性疾病的关系。

Stem cell source-dependent reconstitution of FOXP3+ T cells after pediatric SCT and the association with allo-reactive disease.

机构信息

Center for Molecular and Cellular Intervention (CMCI), University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Bone Marrow Transplant. 2013 Apr;48(4):502-7. doi: 10.1038/bmt.2012.174. Epub 2012 Sep 24.

Abstract

In adult patients, regulatory CD4+FOXP3+ T cells are suggested to have a role in the control of allo-reactive disease after hematopoietic SCT (HSCT). We compared CD4+FOXP3+ T-cell reconstitution after unrelated cord blood (UCB), matched unrelated donor (MUD) and matched sibling donor (MSD) HSCT in children, starting as early as 1 week after transplantation, and analyzed the association with allo-reactive disease. A total of 30 children were included who underwent a myeloablative-conditioning regimen followed by UCB (12/30), MUD (7/30) or MSD (11/30) HSCT. These three patient groups showed significant differences in FOXP3+ T-cell reconstitution pattern. Early after UCB and MSD, but not after MUD, HSCT a peak in FOXP3+ T cells was observed. There were significant differences in activation status and Ki67 expression of the FOXP3+ T cells after UCB and MSD, respectively. FOXP3+ T-cell proportions early after HSCT and in the graft were inversely correlated with allo-reactivity. This study indicates that FOXP3 reconstitution after HSCT is dependent on the type of graft used. Furthermore, in children evaluation of FOXP3+ T-cell numbers early after HSCT and in the graft may be used to judge the risk of developing allo-reactivity after HSCT.

摘要

在成人患者中,调节性 CD4+FOXP3+T 细胞被认为在造血干细胞移植(HSCT)后控制同种异体反应性疾病中发挥作用。我们比较了儿童接受无关脐带血(UCB)、匹配无关供体(MUD)和匹配同胞供体(MSD)HSCT 后 CD4+FOXP3+T 细胞重建情况,最早在移植后 1 周进行,分析其与同种异体反应性疾病的关联。共纳入 30 例接受清髓性预处理方案后接受 UCB(12/30)、MUD(7/30)或 MSD(11/30)HSCT 的儿童。这三组患者的 FOXP3+T 细胞重建模式存在显著差异。在 UCB 和 MSD 后早期,但在 MUD 后早期,观察到 FOXP3+T 细胞的峰值。UCB 和 MSD 后 FOXP3+T 细胞的激活状态和 Ki67 表达存在显著差异。HSCT 后早期和移植物中 FOXP3+T 细胞的比例与同种异体反应性呈负相关。本研究表明,HSCT 后 FOXP3 重建取决于移植物的类型。此外,在儿童中,HSCT 后早期和移植物中 FOXP3+T 细胞数量的评估可用于判断 HSCT 后发生同种异体反应的风险。

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