ORIGINAL ARTICLE: The Persistence of Paternal Antigens in the Maternal Body is Involved in Regulatory T‐Cell Expansion and Fetal‐Maternal Tolerance in Murine Pregnancy

Citation Zenclussen ML, Thuere C, Ahmad N, Wafula PO, Fest S, Teles A, Leber A, Casalis PA, Bechmann I, Priller J, Volk H‐D, Zenclussen AC. The persistence of paternal antigens in the maternal body is involved in regulatory T‐cell expansion and fetal‐maternal tolerance in murine pregnancy. Am J Reprod Immunol 2010; 63: 200–208 Problem Mammalian pregnancy is a state of immunological tolerance and CD4⁺ CD25⁺ regulatory T cells (Treg) contribute to its maintenance. Knowing that Treg act in an antigen‐specific way during pregnancy, we hypothesized that they are generated after maternal immune cells encounter paternal antigens. Method of study We mated wild type females with transgenic green fluorescent protein (GFP) males in an allogenic setting and killed them on different days of pregnancy. Results Presence of paternal and maternal MHC class II⁺ cells in vaginal lavage on day 0.5 of pregnancy was confirmed. Thus, antigen presentation may take place early during pregnancy in the periphery either by the direct or indirect pathways. Foxp3⁺ cells known to have regulatory activity could be detected on day 2 of pregnancy in lymph nodes and shortly after implantation at the fetal‐maternal interface. Conclusion Our data suggest that paternal antigens are processed early during pregnancy, which leads to the generation of Treg. The continuous release of placental antigens into the maternal circulation allows the maintenance of a Treg population which is specific for paternal antigens and mediates tolerance toward the semi‐allogeneic fetus until the time point of birth.