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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 (p < 0.001). Expressed as genome equivalents (gEq) per 105 total gEq tested (gEq/105), memory T cell MMc averaged 850.2 gEq/105, while other subset mean quantities were 13.8–30.1 gEq/105. 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 vivo 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.
Disclosure of potential conflicts of interest
JLN conceived the study, SBK, SCD, and JLN designed the experiments. SBK, AMF and EC performed the experiments. SBK, HSG, WH, PAS, SCD, JA, KB, CSD, and JLN analyzed the data and critically contributed to paper drafting. SBK wrote the paper. The authors declare no competing financial interests.
Acknowledgments
The authors thank all of the study subjects and families for their participation in this research.
Funding
This research was supported by the Thrasher Research Fund, and the National Institutes of Health by grants R01 HL117737, K08HD067221, and T32 HD007233.