Maternal and Fetal Factors that Contribute to the Localization of T Regulatory Cells During Pregnancy

Problem: To determine the interplay between fetal antigenicity and local maternal factors in determining reproductive tract T regulatory (Treg) cell accumulation during pregnancy. Method of study: Examination of maternal Treg composition in the uterus, cervix, and uteroplacental interface (UPI) of murine syngeneic and allogeneic pregnancies and non-pregnant controls by flow cytometry. The impact of fetal antigenicity was defined by either fetal gender in syngeneic pregnancies or by allogeneic paternity. Impact of IL-6 on local Treg composition was determined using syngeneic pregnancies in IL-6^(−/−) females. Results: An increased fraction of CD4^+ T cells in the pregnant uterine lymphocytic infiltrate and draining pelvic lymph nodes are Tregs. Maternal IL-6 decreases Treg accumulation within the uterus and to a greater extent in the cervix in syngeneic pregnancy. Fetal antigenicity is matched by accumulation of Tregs to the UPI. Treg accumulation at the UPI of non-antigenic female fetuses is determined by the intrauterine position relative to male siblings. Conclusion: Reproductive tract tissue Treg composition during pregnancy is influenced by maternal IL-6 and fetal antigenicity.