Human amniotic epithelial cells inhibit activation and pro-inflammatory cytokines production of naive CD4+ T cells from women with unexplained recurrent spontaneous abortion

Abstract

Unexplained recurrent spontaneous abortion (URSA) has been assumed to be caused by a defect in maternal immunological tolerance to the fetus. Human amniotic epithelial cells (hAECs) have stem cell-like features and the ability to modulate the innate and adoptive immune responses. This study aimed to investigate whether hAECs have immunomodulatory effects on naive CD4+ T cells from URSA patients. hAECs were obtained from 15 healthy pregnant women and phenotypic profile of hAECs was determined by flow cytometry. Naive CD4+ T cells were isolated from 25 URSA patients using an immunomagnetic separation method. Naive T cells were stimulated with anti-CD3/anti-CD28 antibodies and co-cultured with different numbers of hAECs for 3 and 6 days. Immunomodulatory effect of hAECs on activation of stimulated T cell was assessed by flow cytometry and Enzyme-linked immunoasorbent assay (ELISA). The hAECs effect on pro-inflammatory cytokines production of activated T cells was also measured by ELISA. Our results indicated that hAECs significantly inhibited the activation of naive T cells in a dose-dependent manner (p < 0.0001-0.05). They significantly reduced the production of transforming growth factor-beta1 (TGF-β1) of stimulated CD4+T cells (p < 0.0001-0.05). Moreover, hAECs had potent immunomodulatory effects on the production of interferon-gamma (IFN-γ) and interleukin-17A (IL-17A) of activated T cells (p < 0.0001-0.01). These findings suggest that hAECs may be a suitable cell source to modulate abnormal immune responses in women with URSA.

Keywords: Amniotic epithelial cells; Naive T cells; Unexplained recurrent spontaneous abortion.