Uterine integrity is required to maintain human fetal immunologic naiveté (MUC7P.770)

Introduction: 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 naive state of the fetal immune system has not been explored thus far. Methods: 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. Results: 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+), specifically 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 FoxP3+ regulatory T cells when the placenta was implanted over the prior uterine scar. Discussion: Our study demonstrates that intrauterine formation of tolerogenic fetal responses is caused by fetal exposure to a scarred uterus. Our results highlight the role that uterine integrity plays as an immunologic barrier.