title: Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells.
abstract: Protective mechanisms are likely to be present at the fetomaternal interface because fetus-specific alloreactive T cells present in the decidua do not harm the fetus. We tested the immunosuppressive capacity of maternal and fetal multipotent stromal cells (MSC). Single cell suspensions were made from second-trimester amnion, amniotic fluid, and decidua. Culture-expanded cells were identified as MSC based on phenotype and multilineage potential. Coculture of MSC in a primary mixed lymphocyte culture of unrelated responder-stimulator combinations resulted in a dose-dependent inhibition of proliferation. Fetal MSC demonstrated a significantly higher inhibition compared with maternal MSC. This stronger inhibition by fetal MSC was even more prominent in a secondary mixed lymphocyte reaction (MLR) with primed alloreactive T cells. Analysis of cytokine production revealed that fetal MSC produced significantly more interleukin (IL)-10 and vascular endothelial growth factor than maternal MSC. Cell-cell contact is needed for part of the inhibitory effects of MSC. In addition, soluble factors play a role because blocking experiments with anti-IL-10 revealed that the inhibition of the MLR response by fetal MSC is mainly mediated by IL-10. For maternal MSC, other soluble factors seem to be involved. Fetal MSC derived from the fetomaternal interface have a stronger inhibitory effect on naive and antigen-experienced T cells compared with maternal MSC, which is probably related to their higher IL-10 production.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. D.L.Roelen@LUMC.nl
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: van der Mast
authors.forename: Pieternella S
authors.initials: PS
authors.lastname: in't Anker
authors.forename: Carin
authors.initials: C
authors.lastname: Kleijburg
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Els
authors.initials: E
authors.lastname: van Beelen
authors.forename: Godelieve M J S
authors.initials: GM
authors.lastname: de Groot-Swings
authors.forename: Wim E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Humphrey H H
authors.initials: HH
authors.lastname: Kanhai
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D037881:Aborted Fetus / Q000166:cytology; D000650:Amnion / Q000166:cytology; D000653:Amniotic Fluid / Q000166:cytology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003656:Decidua / Q000166:cytology; D005260:Female; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines