骨髓增生异常综合征患者间充质干细胞对T细胞的免疫抑制作用

Immuno-suppressive Effects on T Cells Mediated by Mesenchymal Stem Cells from Patients with Myelodysplastic Syndrome

本研究比较来源于正常志愿者和骨髓增生异常增生综合症-难治性贫血(MDS-RA)患者骨髓间充质干细胞(MSC)免疫抑制作用的区别。培养12例正常志愿者和12例MDS患者的骨髓MSC,比较两组MSC的形态、细胞表型、细胞因子的表达,通过植物血凝素(PHA)刺激的T细胞增殖试验、混合淋巴细胞反应和T细胞周期检测、T细胞凋亡检测等比较两组MSC对T细胞的抑制作用的区别。结果表明:两组MSC的形态、表型基本相同;MDS患者来源的MSC对PHA和同种异体抗原诱导的T细胞的抑制作用均低于正常志愿者来源的MSC;加入正常志愿者的MSC后有更多的T细胞阻滞在G0/G1期,但MDS来源的MSC的这种作用较弱;MDS来源的MSC抑制T细胞活化的能力也下降,但是抑制T细胞凋亡的能力增强。另外,MDS来源的MSC表达转化生长因子(TGF-β1、3)、FasL较正常志愿者MSC表达的明显减弱,而TGF-β2的表达却增加。结论:虽然MDS来源的MSC在形态、增殖和细胞表型上基本正常,但其对T细胞的抑制作用减弱,其异常是否与MDS的发病机制有关需要进一步的研究。

The study was aimed to compare the effects of T-cell suppression mediated by mesenchymal stem cells （MSC） from normal individuals and myeledysplastic syndromes （MDS） patients. MSC were cultured from the bone marrow of 12 healthy volunteers and 12 MDS patients, the morphology, surface markers and expression of serveral cytokines of MSC from normal individuals and MDS patients were compared, and the effects of T-cell supression were tested in the following assays： phytohemaglutinin （PHA） -primed cultures, mixed lymphocyte reaction （ MLR）, cell cycle of T-cell after PHA-primed cultures and apoptosis of T-cell as well. The results showed that the MSC from normal individuals and MDS patients were similar in morphology, proliferation and surface markers, The suppressions of T-cell proliferation induced by PHA and alloantigens mediated by MDS-MSC were significantly lower than that of normal MSC. More T-cells were arrested in G0/G1 phase by normal MSC, while the effects were deficient by MDS-MSC. The suppression of T-cell activation mediated by MDS-MSC was also lower than that of normal MSC, but suppression effect on T-cell apoptosis increased. The cytokines TGF-β1, 3, FasL expressed by MDS-MSC were reduced as compared with normal MSC, but TGF-β2 expression increased in MDS-MSC. It is concluded that although the morphology, proliferation and cell surface markers of MDS-MSC are normal, the T-cell suppression mediated by MDS-MSC is deficient as compared with normal controls. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined.