Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
Stem Cells Dev. 2011 Dec;20(12):2115-26. doi: 10.1089/scd.2011.0031. Epub 2011 Apr 19.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells exerting immunomodulatory effects on cells of the innate and adaptive immune system. It has been shown that an inflammatory milieu is required for the activation of MSC-mediated immunomodulation, and interferon-γ (IFN-γ) plays an important role in this process. We determined the influence of IFN-γ on human adipose-derived stem cells (ASCs) and human amniotic mesenchymal stromal cells (hAMSCs). We further evaluated the effect of MSCs on stimulated T-cells and peripheral blood mononuclear cells (PBMCs) in a cell-contact independent setting. On IFN-γ treatment, ASCs and hAMSCs possessed significantly higher antiproliferative properties and showed surface characteristics of nonprofessional antigen presenting cells (HLA-DR(+)CD40(med+)CD54(high)) with a possible regulatory phenotype (PD-L1(+)PD-L2(+)). The effect of ASCs and hAMSCs on cytokine secretion and T-cell activation was dependent on stimulation method and cellular context. Although ASCs and hAMSCs highly inhibited cytokine secretion of stimulated PBMCs, this was not observed in the case of purified T-cells. The presence of ASCs even favored the secretion of pro-inflammatory cytokines including IFN-γ by T-cells, although T-cell proliferation was efficiently inhibited. Further, ASCs enhanced the number of CD69(+) T-cells independent of the stimuli and cellular context. Interestingly, ASCs significantly suppressed CD25 expression on phytohemagglutinin stimulated PBMCs but had no effect on αCD3/αCD28 stimulated cells. Depending on the stimulation method and cellular context, immune cells create a specific cytokine milieu in vitro, thus differently influencing MSCs and, in turn, affecting their action on immune cells.
间充质干细胞（MSCs）是多能祖细胞，对固有和适应性免疫系统的细胞具有免疫调节作用。已经表明，激活 MSC 介导的免疫调节需要炎症环境，干扰素-γ（IFN-γ）在这个过程中起着重要作用。我们确定了 IFN-γ对人脂肪来源干细胞（ASCs）和人羊膜间充质基质细胞（hAMSCs）的影响。我们进一步评估了 MSC 在非细胞接触的情况下对刺激的 T 细胞和外周血单核细胞（PBMCs）的影响。在 IFN-γ 处理下，ASCs 和 hAMSCs 具有明显更高的抗增殖特性，并表现出非专业抗原呈递细胞的表面特征（HLA-DR(+)CD40(med+)CD54(high)），具有可能的调节表型（PD-L1(+)PD-L2(+)）。ASCs 和 hAMSCs 对细胞因子分泌和 T 细胞激活的影响取决于刺激方法和细胞环境。尽管 ASCs 和 hAMSCs 高度抑制刺激的 PBMCs 的细胞因子分泌，但在纯化的 T 细胞中未观察到这种情况。尽管 T 细胞增殖被有效抑制，但 ASCs 的存在甚至有利于包括 IFN-γ在内的促炎细胞因子的分泌。此外，ASCs 独立于刺激物和细胞环境增强 CD69(+)T 细胞的数量。有趣的是，ASCs 显著抑制植物血凝素刺激的 PBMCs 上的 CD25 表达，但对 αCD3/αCD28 刺激的细胞没有影响。根据刺激方法和细胞环境的不同，免疫细胞在体外创造特定的细胞因子环境，从而不同地影响 MSC，并进而影响它们对免疫细胞的作用。
