JEG-3 Trophoblast Cells Producing Human Chorionic Gonadotropin Promote Conversion of Human CD4+FOXP3- T Cells into CD4+FOXP3+ Regulatory T Cells and Foster T Cell Suppressive Activity

Abstract

The pregnancy hormone human Chorionic Gonadotropin (hCG) reportedly modulates innate and adaptive immune responses and contributes thereby to fetal survival. More precisely, hCG has been shown to support human Treg cell homing into the fetal-maternal interface and enhance number and function of Treg cells in murine pregnancy. Here, we aimed to study whether hCG and hCG-producing human trophoblast cell lines induce Treg cells from CD4⁺FOXP3^- T cells and promote T cell suppressive activity. CD4⁺FOXP3^- T cells were isolated from peripheral blood of normal pregnant women and cultured in the presence of hCG-producing (JEG-3, HTR-8) and non-producing (SWAN-71) cell lines. To confirm the participation of hCG in Treg cell conversion, the experiments were performed in the presence of anti-hCG and additional experiments were run with recombinant or urine-purified hCG. After culture the number of CD4⁺FOXP3⁺ Treg cells as well as the suppressive capacity of total T cells was assessed. hCG-producing JEG-3 cells as well as recombinant and urine-purified hCG induced CD4⁺FOXP3⁺ Treg cells from CD4⁺FOXP3^- T cells. Blockage of hCG impaired Treg cell induction. Moreover, hCG-producing JEG-3 cells increased suppressive activity of CD4⁺FOXP3^- T cells through an antigen-independent pathway. Our results propose another mechanism through which hCG modulates the female immune system during pregnancy in favor of the fetus.

Keywords: Gonadotropins; Human chorionic gonadotropin (hCG / hCG receptor); Human reproduction; Immunology; Trophoblast.