Department of Immunology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
PLoS One. 2011 Jan 11;6(1):e16005. doi: 10.1371/journal.pone.0016005.
Mesenchymal stromal cells (MSC) have important immunomodulatory effects that can be exploited in the clinical setting, e.g. in patients suffering from graft-versus-host disease after allogeneic stem cell transplantation. In an experimental animal model, cultures of rat T lymphocytes were stimulated in vitro either with the mitogen Concanavalin A or with irradiated allogeneic cells in mixed lymphocyte reactions, the latter to simulate allo-immunogenic activation of transplanted T cells in vivo. This study investigated the inhibitory effects of rat bone marrow-derived MSC subsequently found to be infected with a common mycoplasma species (Mycoplasma hyorhinis) on T cell activation in vitro and experimental graft-versus-host disease in vivo.
We found that M. hyorhinis infection increased the anti-proliferative effect of MSC dramatically, as measured by both radiometric and fluorimetric methods. Inhibition could not be explained solely by the well-known ability of mycoplasmas to degrade tritiated thymidine, but likely was the result of rapid dissemination of M. hyorhinis in the lymphocyte culture.
This study demonstrates the potent inhibitory effect exerted by M. hyorhinis in standard lymphocyte proliferation assays in vitro. MSC are efficient vectors of mycoplasma infection, emphasizing the importance of monitoring cell cultures for contamination.
间充质基质细胞(MSC)具有重要的免疫调节作用,可在临床环境中得到利用,例如在接受同种异体干细胞移植后发生移植物抗宿主病的患者中。在实验动物模型中,体外刺激大鼠 T 淋巴细胞培养物,要么使用丝裂原刀豆蛋白 A,要么在混合淋巴细胞反应中使用辐照同种异体细胞,后者模拟体内移植 T 细胞的同种免疫激活。本研究调查了随后发现感染常见支原体物种(猪鼻支原体)的大鼠骨髓来源 MSC 对体外 T 细胞活化和体内实验性移植物抗宿主病的抑制作用。
我们发现,猪鼻支原体感染极大地增加了 MSC 的抗增殖作用,这可以通过放射性和荧光测量方法来衡量。抑制作用不能仅用支原体降解氚胸腺嘧啶的已知能力来解释,而可能是由于支原体在淋巴细胞培养物中的快速传播所致。
本研究证明了猪鼻支原体在体外标准淋巴细胞增殖测定中的强大抑制作用。MSC 是支原体感染的有效载体,强调了监测细胞培养物污染的重要性。