Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells.
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.
Roelen
Dave L
DL
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. D.L.Roelen@LUMC.nl
van der Mast
Barbara J
BJ
in't Anker
Pieternella S
PS
Kleijburg
Carin
C
Eikmans
Michael
M
van Beelen
Els
E
de Groot-Swings
Godelieve M J S
GM
Fibbe
Wim E
WE
Kanhai
Humphrey H H
HH
Scherjon
Sicco A
SA
Claas
Frans H J
FH
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
D016207:Cytokines