The immunomodulating effect of semen on maternal T cells

Introduction: Semen contains a variety of immunoregulatory factors that may play an important role in the creation of a tolerogenec environment at the implantation site leading to normal pregnancy. The aim of this studywas to investigate the influence of seminal plasma onmaternal peripheral blood mononuclear cells (mPBMCs). Method: First, the direct effect of semen on mPBMCs was measured by incubating these with semen of different sperm quality. Second, to simulate implantation where the immune system of the mother meets her semiallogeneic fetus, mPBMCs were stimulated with paternal PBMCswith one HLA-DRmismatch in amixed lymphocyte culture in theabsenceandpresenceof semen. Furthermore, supernatants were harvested at day 5 and cytokine concentrations were determined using the Luminex method. In addition, mRNA analysis was performed to measure the immediate effect of semen on mPBMCs. Results: Maternal cells showed a significant proliferation and cytokine production when semen was added. In particular, IL-10, IL-17, IL-2, TNF-a, and Il-1b were produced in large amounts bymaternal cells in the presence of semen. Additional mRNA analysis showed a quick and significant upregulation of CD25 and IL-10 in T-cells under the influence of semen. Semen had a differential effect on the immune responseofmaternal cells to allogeneic stimulator cells. Both an increased and decreased MLC response was observed. So far no factors could be identified, explaining this different effect of semen on the alloimmune response. Conclusion: Semen has a direct effect on maternal T cells as reflected by a proliferative response and the secretion of cytokines. Upregulation of both CD25 and IL-10 mRNA by the addition of semen suggests the induction of amore regulatory phenotype of the immune response. The absence of immunoregulatory function and/or less exposure to semen may be the underlying cause in abnormal implantation and lead to complicated pregnancies.