title: Human chorionic gonadotropin as a central regulator of pregnancy immune tolerance.
abstract: Normal pregnancy is characterized by an early expansion of regulatory T cells (Tregs), which is known to contribute to fetal tolerance. However, mechanisms and factors behind Treg expansion are not yet defined. Recently, we proposed that the pregnancy hormone human chorionic gonadotropin (hCG) efficiently attracts human Tregs to trophoblasts, favoring their accumulation locally. In this study, we hypothesized that hCG not only acts as a chemoattractant of Tregs but also plays a central role in pregnancy-induced immune tolerance. Virgin, normal pregnant, and abortion-prone female mice were treated either with 10 IU/ml hCG or PBS at days 0, 2, 4, and 6 of pregnancy. The hCG effect on Treg frequency and cytokine secretion was determined in Foxp3(gfp) females. hCG impact on Treg suppressive capacity was studied in vitro. In vivo, we investigated whether hCG enhances Treg suppressive capacity indirectly by modulating dendritic cell maturation in an established mouse model of disturbed fetal tolerance. Application of hCG increased Treg frequency in vivo and their suppressive activity in vitro. In females having spontaneous abortions, hCG provoked not only an augmentation of Treg numbers, but also normalized fetal abortion rates. hCG-generated Tregs were fully functional and could confer tolerance when adoptively transferred. hCG also retained dendritic cells in a tolerogenic state that is likely to contribute to both Treg expansion and prevention of abortion. Our results position hCG in a novel, so far unknown role as modulator of immune tolerance during pregnancy.
authors: Department of Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, Germany.
authors: Anne
authors: A
authors: Schumacher
authors: Kristina
authors: K
authors: Heinze
authors: Jeanette
authors: J
authors: Witte
authors: Eileen
authors: E
authors: Poloski
authors: Nadja
authors: N
authors: Linzke
authors: Katja
authors: K
authors: Woidacki
authors: Ana C
authors: AC
authors: Zenclussen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000502:physiology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011247:Pregnancy / Q000276:immunology*; D011257:Pregnancy Proteins / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; D011257:Pregnancy Proteins