Endocrine Abstracts

Introduction: Human Chorionic Gonadotropin (hCG) contributes to fetal tolerance by regulating innate and adaptive immune responses during pregnancy. Our previous results suggested a pregnancy protective effect of hCG through enhancement of regulatory T (Treg) cells and inhibition of dendritic cell (DC) maturation. Here, we aimed to investigate whether hCG contributes to Treg generation by modulating DC phenotype in vitro and in vivo in a murine model.

Methods: Bone marrow-derived DCs (BMDCs) from virgin CBA/J female mice were in vitro stimulated with LPS and IFN-γ to induce maturation. In parallel, BMDCs were cultured in the presence of various concentrations of urine-purified or recombinant hCG. After 24 and 48 h the BMDCs were analyzed for their maturation state and cytokine secretion pattern. Additionally, BMDCs were analyzed for their capability to induce the differentiation of naïve T cells into TH1, TH2 or Treg cells.

Moreover, hCG- and non hCG-treated stimulated BMDCs were adoptively transferred into abortion-prone mice to evaluate their in vivo function. On pregnancy day 12 the pregnancy outcome as well as the peripheral and local number of Treg cells was determined.

Results: BMDC stimulation resulted in a significant increase in the number of mature BMDCs and in secretion of TH1 and TH2 cytokines. Both hCG preparations significantly impaired the ability of BMDCs to mature but did not significantly influence cytokine secretion. As for their function, recombinant hCG-treated BMDCs had a reduced potential to induce TH1 or Th2 cells but could increase the number of Treg cells. In vivo, the transfer of hCG-treated BMDCs increased the number of peripheral and local Treg cells and protected fetuses from immunological abortion.

Conclusions: Our results reveal that hCG contributes to Treg-mediated fetal protection by modulating the phenotype of DCs.