Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
J Immunother. 2011 May;34(4):336-42. doi: 10.1097/CJI.0b013e318217007c.
Multipotent mesenchymal stromal cells (MSCs) have immunosuppressive capacity but the exact mechanism by which they suppress proliferation of T lymphocytes is not fully understood. Recently, the characteristics and function of regulatory T lymphocytes (Tregs) have become better defined. Tregs and MSCs have immunosuppressive features in common. Here, we looked for a common basis for immunosuppression in these distinct cell types. Forkhead box P3 (FoxP3) and CD39 expression in MSCs was measured by flow cytometry and real-time quantitative polymerase chain reaction. The importance of FoxP3 in MSC-mediated immunosuppression was investigated by siRNA technology and mixed lymphocyte culture (MLC). The effect of 5-azacytidine and other immunosuppressive drugs on FoxP3 expression and immunosuppression by MSCs was explored by flow cytometry, MLC, and real-time quantitative polymerase chain reaction. MSCs express FoxP3 at variable levels, but they do not express CD39. FoxP3 MSCs suppress MLC to a greater extent than cells with lower FoxP3 expression. However, FoxP3-decreased MSCs were found to retain their immunosuppressive properties. 5-azacytitine had no effect on FoxP3 expression or MLC suppression by MSCs. However, immunosuppressive drugs led to increased FoxP3 levels and MLC inhibition in FoxP3 MSCs. This is the first demonstration of FoxP3 expression by MSCs. Although MSCs share several features with Tregs, and FoxP3 MSCs tend to be more immunosuppressive, MSCs do not require functional FoxP3 for their immunosuppressive activity. The increased MSC-mediated suppression of immune responses by immunosuppressive drugs deserves further investigation.
多能间充质基质细胞 (MSCs) 具有免疫抑制能力，但它们抑制 T 淋巴细胞增殖的确切机制尚未完全阐明。最近，调节性 T 淋巴细胞 (Tregs) 的特征和功能变得更加明确。Tregs 和 MSCs 具有共同的免疫抑制特征。在这里，我们寻找这些不同细胞类型免疫抑制的共同基础。通过流式细胞术和实时定量聚合酶链反应测量 MSCs 中的叉头框 P3 (FoxP3) 和 CD39 表达。通过 siRNA 技术和混合淋巴细胞培养 (MLC) 研究 FoxP3 在 MSC 介导的免疫抑制中的重要性。通过流式细胞术、MLC 和实时定量聚合酶链反应探索 5-氮杂胞苷和其他免疫抑制药物对 FoxP3 表达和 MSC 免疫抑制的影响。MSCs 以不同的水平表达 FoxP3，但不表达 CD39。FoxP3 MSC 比表达较低 FoxP3 的细胞更能抑制 MLC。然而，发现 FoxP3 减少的 MSC 仍然保留其免疫抑制特性。5-氮杂胞苷对 FoxP3 表达或 MSCs 对 MLC 的抑制没有影响。然而，免疫抑制药物导致 FoxP3 MSC 中 FoxP3 水平升高和 MLC 抑制增加。这是首次证明 MSCs 表达 FoxP3。尽管 MSCs 与 Tregs 具有一些共同特征，并且 FoxP3 MSC 往往更具免疫抑制性，但 MSCs 不需要功能性 FoxP3 来发挥其免疫抑制活性。免疫抑制药物增加 MSC 介导的免疫反应抑制作用值得进一步研究。
