Human chorionic gonadotropin supports human pregnancy by induction of regulatory T cells (MUC7P.766)

Abstract

Abstract Regulatory T cells (Treg) are proposed to be involved in fetal tolerance induction. However, the precise mechanisms underlying their generation and function are still not defined. Recently, we proved that the pregnancy hormone human Chorionic Gonadotropin (hCG) efficiently attracts human Treg to trophoblasts favoring a local Treg accumulation. Here we analyzed whether hCG is also involved in Treg generation and activity. Naïve T cells were isolated from blood of pregnant women and co-cultured with either hCG-producing trophoblasts (JEG-3, primary cells) or non-hCG-producing trophoblasts (HTR8, Swan71) and keratinocytes (HaCat). To confirm hCG specificity, we either blocked hCG in JEG-3 co-cultures or used urine-purified or recombinant hCG as culture supplements. Treg induction was then assessed by the expression of specific Treg markers. Furthermore suppressive function of hCG-treated naïve T cells was evaluated in a mixed leukocyte reaction. Co-culture of naïve T cells with JEG-3, primary trophoblasts or supplemented hCG resulted in a statistically significant increase in the expression of specific Treg markers as compared to co-cultures with HTR8, Swan71 or HaCat cells. Moreover, blockage of hCG in JEG-3 co-cultures impaired the up-regulation of Treg markers. Interestingly, we further confirmed an increased suppressive activity of naïve T cells after hCG treatment. Our results strongly suggest a key role for hCG in Treg generation and induction of suppressive activity.