Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Transpl Immunol. 2011 Jul;25(1):7-15. doi: 10.1016/j.trim.2011.05.004. Epub 2011 May 23.
Although both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) are known to have immunosuppressive effects, the mechanisms of immunosuppression are still controversial. Both types of stem cells suppressed not only the proliferation but also survival of CD4(+) T cells in vitro. They suppressed secretion of various cytokines (IL-2, IL-12, IFN-γ, TNF-α, IL-4, IL-5, IL-1β, and IL-10), whereas there was no change in the levels of TGF-β or IDO. Classic and modified transwell experiments demonstrated that immunosuppressive activities were mainly mediated by cell-to-cell contact. Granzyme B in the ESCs played a significant role in their immunosuppression, whereas PDL-1, Fas ligand, CD30 or perforin was not involved in the contact-dependent immunosuppression. However, none of the above molecules played a significant role in the immunosuppression by the MSCs. Interestingly, both stem cells increased the proportion of Foxp3(+) regulatory T cells. Our results showed that both ESCs and MSCs suppressed the survival as well as the proliferation of T cells by mainly contact-dependent mechanisms and increased the proportion of regulatory T cells. Granzyme B was involved in immunosuppression by the ESCs in a perforin-independent manner.
虽然胚胎干细胞 (ESCs) 和间充质干细胞 (MSCs) 都具有免疫抑制作用，但免疫抑制的机制仍存在争议。这两种类型的干细胞不仅抑制了 CD4(+) T 细胞的增殖，还抑制了其存活。它们抑制了各种细胞因子（IL-2、IL-12、IFN-γ、TNF-α、IL-4、IL-5、IL-1β 和 IL-10）的分泌，而 TGF-β 或 IDO 的水平没有变化。经典和改良的 Transwell 实验表明，免疫抑制活性主要通过细胞间接触介导。ESCs 中的颗粒酶 B 在其免疫抑制中起重要作用，而 PDL-1、Fas 配体、CD30 或穿孔素则不参与依赖接触的免疫抑制。然而，上述分子在 MSC 的免疫抑制中均未发挥重要作用。有趣的是，两种干细胞均增加了 Foxp3(+)调节性 T 细胞的比例。我们的研究结果表明，ESCs 和 MSCs 主要通过依赖接触的机制抑制 T 细胞的存活和增殖，并增加调节性 T 细胞的比例。颗粒酶 B 在不依赖穿孔素的情况下通过 ESCs 发挥免疫抑制作用。
