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- W2132504399 abstract "In healthy pregnancy, maternal and fetal compartments are physically separated by multiple cell layers and the fetal immune system displays an ‘in-experienced’ phenotype in utero. The uterus as an immunologic barrier contributing to the naïve state of the fetal immune system has not been explored thus far. Memory vs. naïve T cells can be distinguished based on the expression of CD45 RO vs. CD45 RA. A prospective cohort study of fetuses born to mothers with prior uterine scar was undertaken (UCLA IRB # 11-002962). Cord blood lymphocytes were analyzed for memory status of the T regulatory cells (CD4+FoxP3+RO/RA) and blinded from placental location prior to final analysis. The degree of maternal microchimerism was determined using qPCR for known insertion-deletions to distinguish maternal DNA from fetal. In vitro suppression of proliferation assays were done using 3[H]-thymidine incorporation. In this prospective cohort study, we identified placental implantation in apposition to a uterine scar as a sufficient factor for fetal in utero immune activation (CD45RO+), especially in the regulatory T cell compartment. Our results (N=20) identify a risk difference of 90% with a relative risk of 10 (p<0.05) of activation (RO+) of the regulatory T cells when the placenta was implanted over the prior uterine scar. The degree of maternal to fetal microchimerism was increased in pregnancies where the placenta was anterior (in contact with scar) vs posterior (0.000998 ± 0.0003801% vs. 0.0001808 ±0.00005501%, p = 0.0290). Fetal RO+ Tregs are functionally superior suppressors to naïve Tregs on a per cell basis. Our study demonstrates that intrauterine formation of tolerogenic fetal responses is caused by fetal exposure to a scarred uterus. Exposure of maternal allogeneic cells is likely the cause of the increased fetal Treg response. Our results highlight the role that uterine integrity plays as an immunologic barrier." @default.
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- W2132504399 date "2015-01-01" @default.
- W2132504399 modified "2023-09-26" @default.
- W2132504399 title "397: Uterine integrity is required to maintain human fetal immunologic naiveté" @default.
- W2132504399 doi "https://doi.org/10.1016/j.ajog.2014.10.443" @default.
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