Sanquin Research, Dept of Hematopoiesis, Amsterdam, The Netherlands, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Sanquin Diagnostics BV, Department of Immunogenetics, Amsterdam, The Netherlands.
Sci Rep. 2019 Mar 27;9(1):5247. doi: 10.1038/s41598-019-41733-w.
During pregnancy, maternal T cells can enter the foetus, leading to maternal-foetal chimerism. This phenomenon may affect how leukaemia patients respond to transplantation therapy using stem cells from cord blood (CB). It has been proposed that maternal T cells, primed to inherited paternal HLAs, are present in CB transplants and help to suppress leukaemic relapse. Several studies have reported evidence for the presence of maternal T cells in most CBs at sufficiently high numbers to lend credence to this idea. We here aimed to functionally characterise maternal T cells from CB. To our surprise, we could not isolate viable maternal cells from CB even after using state-of-the-art enrichment techniques that allow detection of viable cells in heterologous populations at frequencies that were several orders of magnitude lower than reported frequencies of maternal T cells in CB. In support of these results, we could only detect maternal DNA in a minority of samples and at insufficient amounts for reliable quantification through a sensitive PCR-based assay to measure In/Del polymorphisms. We conclude that maternal microchimerism is far less prominent than reported, at least in our cohort of CBs, and discuss possible explanations and implications.
在妊娠期间,母体 T 细胞可进入胎儿,导致母婴嵌合体。这种现象可能会影响白血病患者对使用脐带血(CB)干细胞进行移植治疗的反应。有人提出,对遗传自父系 HLA 的抗原具有初始致敏作用的母体 T 细胞存在于 CB 移植中,并有助于抑制白血病复发。几项研究报告了在大多数 CB 中存在足够数量的母体 T 细胞的证据,这为这一观点提供了依据。我们在此旨在从 CB 中对母体 T 细胞进行功能特征分析。令我们惊讶的是,即使使用了最先进的富集技术,这些技术允许在异质群体中以比报道的 CB 中母体 T 细胞频率低几个数量级的频率检测到有活力的细胞,我们仍无法从 CB 中分离出有活力的母体细胞。这些结果支持我们的观点,我们只能在少数样本中检测到母体 DNA,并且通过基于 PCR 的敏感检测方法检测到的数量不足以进行可靠的定量,以测量插入/缺失多态性。我们的结论是,至少在我们的 CB 队列中,母体微嵌合体远没有报道的那么明显,并讨论了可能的解释和影响。