title: Human Umbilical Vein Endothelial Cells foster conversion of CD4+CD25-Foxp3- T cells into CD4+Foxp3+ Regulatory T Cells via Transforming Growth Factor-β.
abstract: Trans-placental cell trafficking is a naturally occurring process during pregnancy that results in the direct recognition of foreign maternal antigens by fetal tissue and vice versa. Immigration of potentially harmful allo-reactive maternal T cells into fetal circulation may provoke anti-fetal immune responses. However, the contact with fetal tissue may favor differentiation of maternal immune cells into cells with a regulatory phenotype. Human Umbilical Vein Endothelial Cells (HUVECs) possess immune-regulating properties and are one of the first fetal cells to get in contact with foreign maternal immune cells. Therefore, here we studied whether HUVECs induce the conversion of maternal T cells into regulatory T (Treg) cells. Moreover, we assessed whether this response is changing according to the sex of the HUVECs. Both female and male HUVECs induced the conversion of maternal T cells into Treg cells which is partially mediated via TGF-β. Female HUVECs showed a stronger capacity to induce Treg cells compared to male HUVECs. Our findings propose that HUVECs contribute to fetal-maternal tolerance by the increase of the Treg cell population. Sex-specific differences in Treg cell induction may partly account for the disparities on the incidence of infectious and autoimmune diseases between both sexes during early childhood.
authors.affiliation: Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Gerhart-Hauptmann-Straße 35, 39108 Magdeburg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Oettel
authors.affiliation: Medical Clinic for Cardiology and Angiology, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany, Charitéplatz 1, 10117 Berlin, Germany.|DZHK (German Center for Cardiovascular Research), partner site Berlin, Oudenarder Straße 16, 13347 Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: Medical Clinic for Cardiology and Angiology, Campus Mitte, Charite - Universitätsmedizin Berlin, Germany, Charitéplatz 1, 10117 Berlin, Germany.|DZHK (German Center for Cardiovascular Research), partner site Berlin, Oudenarder Straße 16, 13347 Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Stangl
authors.affiliation: University Women's Clinic, Otto-von-Guericke University, Gerhart-Hauptmann-Straße 35, 39108 Magdeburg, Germany.
authors.forename: Serban-Dan
authors.initials: SD
authors.lastname: Costa
authors.affiliation: Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Gerhart-Hauptmann-Straße 35, 39108 Magdeburg, Germany.
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Zenclussen
authors.affiliation: Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Gerhart-Hauptmann-Straße 35, 39108 Magdeburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schumacher
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta