间充质干细胞对系统性红斑狼疮T淋巴细胞的免疫调节作用

Immunosuppressive effects of allogeneic human mesenchymal stem cells on T lymphocytes from patients with systemic lupus erythematosus

目的研究正常健康捐献者骨髓来源的间充质干细胞(MSC)对系统性红斑狼疮(SLE)患者来源的T淋巴细胞的免疫调节作用。方法共培养MSC与正常对照或SLE患者来源的T淋巴细胞,检测MSC对T细胞的作用,包含T细胞增殖能力,细胞表型及其产生的细胞因子等。实验分为健康对照组(C组)与SLE组(S组)。每一大组又分为T细胞组(C1组、S1组)、T细胞+植物血凝素组(C2组、S2组)、T细胞+植物血凝素+MSC组(C3组、S3组)。结果 MSC能抑制SLE患者来源的T淋巴细胞增殖[S2:(2 615.7±582.3)cpm;S3:(784.7±417.5)cpm;P<0.05],促使SLE T细胞向调节性CD4+CD25+Foxp3+T细胞转化增加(S2:11.85%±1.99%;S3:24.17%±5.82%,P<0.05)。MSC还能促使SLE T细胞分泌IFN-γ[S2:(14.13±11.16)pg/ml;S3:(39.68±26.73)pg/ml,P<0.05]与IL-10[S2:(5.09±2.96)pg/ml;S3:(17.15±3.61)pg/ml,P<0.05]。结论 MSC能抑制SLE患者来源的T细胞增殖,促进T细胞向调节性T细胞转化,诱导免疫耐受,有望成为治疗SLE的细胞疗法。

This study designed to investigate the immunosuppressive effects of mesenchymal stem cells （MSCs） on T cells from patients with systemic lupus erythematosus （SLE）. MSCs were isolated and expanded from the bone marrow of healthy donors, and then co-cultured with T cells purified from the peripheral blood of healthy donors or patients with SLE. The statistical analysis were performed by SPSS12.0 using a Student＇ s t-test. The results showed that SLE T-cell proliferation were suppressed by MSCs （FST＋PHA： （2615.7±582.3）cpm; FST＋PHA＋MSC：（784.7±417.5）cpm;P〈0.05）; MSCs could polarize T ceils into regulatory T cells （Treg）, and thus elevate the proportion of CD4^＋CD25^＋ Foxp3^＋T cells （FST＋PHA： 11.85%±1.99%; FST＋PHA＋MSC： 24.17%_＋5.82%, P〈0.05）. Furthermore, MSCs also could up-regulate the level of IFN-γ （FST： （14.13± 11.16） pg/ml; FST＋MSC： （39.68±26.73） pg/ml, P〈0.05） and IL-10 （FST： （5.09±2.96） pg/ml; FST ＋MSC： （17.15±3.61） pg/ml, P〈0.05）. In conclusion, MSCs are capable of suppressing T cell proliferation, and polarizing T cells into Tregs. These data offers insight into the interactions between allogeneic MSC and abnormal T lymphocytes in patients with SLE, provides information for using MSC as cell therapy on treating SLE and other alike autoimmune diseases.