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
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Oncoimmunology. 2017 Mar 31;6(5):e1311436. doi: 10.1080/2162402X.2017.1311436. eCollection 2017.
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.
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。
