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母源微嵌合体在脐带血的记忆T细胞和其他细胞亚群中普遍存在,并在移植后持续存在。

Maternal microchimerism is prevalent in cord blood in memory T cells and other cell subsets, and persists post-transplant.

作者信息

Kanaan Sami B, Gammill Hilary S, Harrington Whitney E, De Rosa Stephen C, Stevenson Philip A, Forsyth Alexandra M, Allen Judy, Cousin Emma, van Besien Koen, Delaney Colleen S, Nelson J Lee

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

出版信息

Oncoimmunology. 2017 Mar 31;6(5):e1311436. doi: 10.1080/2162402X.2017.1311436. eCollection 2017.

Abstract

Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs. Polymorphism-specific quantitative-PCR assays targeted maternal genotypes non-shared with CBs. Overall MMc was common and often at substantial levels. It was present in 52.9% of CB and in 33.3-55.6% of tested subsets. Remarkably, MMc quantities were greater in memory T cells than other subsets ( < 0.001). Expressed as genome equivalents (gEq) per 10 total gEq tested (gEq/10), memory T cell MMc averaged 850.2 gEq/10, while other subset mean quantities were 13.8-30.1 gEq/10. After adjustment for proportionality in CB, MMc remained 6-17 times greater in memory T, and 3-9 times greater in naïve T, vs. non-T-cell subsets. Further, CB-origin MMc was detected in a patient up to 6 mo post-transplantation, including among T cells. Overall, results revealed levels and phenotypes of CB MMc with potential relevance to CB transplantation and, more broadly, to offspring health.

摘要

脐带血(CB)移植的诸多优势中,白血病复发概率较低是其中之一。移植物抗白血病(GVL)的潜在细胞机制被认为T细胞起主要作用。CB供者母亲的细胞,即母源微嵌合体(MMc),最近被强烈但间接认为与这种GVL益处有关。我们直接检测了MMc,并推测益处源于CB母源T细胞。对51份CB进行了MMc定量分析,并对27份CB中的记忆T细胞、初始T细胞、B细胞、NK细胞和单核细胞进行了定量分析。多态性特异性定量PCR检测针对与CB不共享的母源基因型。总体而言,MMc很常见,且通常水平较高。它存在于52.9%的CB中,以及33.3 - 55.6%的检测亚群中。值得注意的是,记忆T细胞中的MMc数量比其他亚群更多(<0.001)。以每10个检测总基因组当量(gEq)中的基因组当量(gEq/10)表示,记忆T细胞MMc平均为850.2 gEq/10,而其他亚群的平均数量为13.8 - 30.1 gEq/10。在对CB中的比例进行调整后,记忆T细胞中的MMc仍比非T细胞亚群高6 - 17倍,初始T细胞中的MMc比非T细胞亚群高3 - 9倍。此外,在一名患者移植后长达6个月时检测到了CB来源的MMc,包括在T细胞中。总体而言,结果揭示了CB MMc的水平和表型,其可能与CB移植以及更广泛的后代健康相关。

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