Background Alloimmunization of women during pregnancy has significant consequences for both transplant access and outcomes. However, the location and context of maternal immune priming by fetal alloantigens during pregnancy is largely unknown. Although protein antigens derived from the fetus and/or placenta disseminate widely and can be presented by maternal antigen presenting cells (APCs), it is unknown whether maternal leukocytes that directly access the fetomaternal interface also play a role in immune priming of T and B cells. Methods To survey for leukocyte populations within the placenta, we performed a longitudinal flow cytometric analysis of placental specimens during murine pregnancy using outbred CD-1 mice to more accurately mimic the semiallogeneic fetus of human pregnancy. To determine whether these placental leukocytes were of fetal or maternal origin, we mated CD45.2 female mice with congenic CD45.1 males such that CD45.2+ maternal leukocytes in the placenta could be discriminated from CD45.2+/CD45.1+ fetal cells. Results At three gestational time points (E12, E15, and E19), we find that Ly6G+ granulocytes (G), F4/80-expressing macrophages (M), and CD19+ B cells (B) are the predominant leukocyte populations in the placenta (G:51-53%; M:12-16%; B:13-21%). CD8+ and CD4+ T cells (including Foxp3+ populations) were present in the placenta throughout gestation but were more infrequent (CD4: 6-7%; CD8: 2%). The distribution of these cells did not significantly change throughout mid to late gestation. However, the frequency of FoxP3+ CD4 cells significantly decreased as gestation approached term, from 14.6% of CD4+ cells at E12 to 2.8% at E19 (p <0.0001). Additionally, using our congenic system, we were able to determine that maternal leukocytes in the placenta outnumbered fetal leukocytes at a ratio of 20:1 (p=0.0023). Conclusion Maternal leukocytes are present in the placenta throughout gestation and consist primarily of B cells and myeloid-derived cells. The biologic role for these cellular populations is currently unknown. Additional studies of the origin of these cells, their migration characteristics, and their ability to present fetal alloantigen to maternal adaptive immune cells will significantly improve our understanding of pregnancy-induced alloimmunization.

CITATION INFORMATION: Porrett P, Lewis E, Xu R, Brown A, Wherry E, Elovitz M. Placental Leukocytes Are Maternally Derived: Implications for Pregnancy-Induced Alloimmunization. Am J Transplant. 2017;17 (suppl 3).

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