Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells

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• 作者：Dave L. Roelen ; Barbara J. van der Mast ; Pieternella S. in't Anker ; Carin Kleijburg ; Michael Eikmans ; Els van Beelen ; Godelieve M.J.S. de Groot-Swings ; Wim E. Fibbe ; Humphrey H.H. Kanhai ; Sicco A. Sch
• 关键词：Multipotent stromal cells ; Stem cells ; T cells ; Pregnancy ; Transplantation
• 刊名：Human Immunology
• 出版年：2009
• 出版时间：January 2009
• 年：2009
• 卷：70
• 期：1
• 页码：16-23
• 全文大小：682 K

文摘

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.