Yang Seung-Ha, Park Min-Jung, Yoon Il-Hee, Kim Su-Young, Hong So-Hee, Shin Jin-Young, Nam Hye-Young, Kim Yong-Hee, Kim Bongi, Park Chung-Gyu
Department of Microbiology and Immunology, Cancer Research Institute, Tumor Immunity Medical Research Center, Xenotransplantation Research Center, Transplantation Research Institute, Seoul National University College of Medicine, Korea.
Exp Mol Med. 2009 May 31;41(5):315-24. doi: 10.3858/emm.2009.41.5.035.
Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either na?ve or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.
间充质干细胞（MSCs）可抑制T细胞增殖；然而，其潜在机制尚不清楚。在本研究中，我们探究了MSCs对T细胞免疫调节活性的机制。在混合淋巴细胞反应（MLR）中，经照射的MSCs与未活化或预活化的T细胞共培养，无论应答者与MSCs之间的同种异体差异如何，均能以剂量依赖的方式显著抑制T细胞增殖。Transwell实验表明，这种抑制作用主要由诱导细胞凋亡的可溶性因子介导。在MSC培养上清液（CS）存在的情况下，用同种异体抗原刺激的脾细胞产生了大量的IL-10，这归因于IL-10分泌细胞数量的增加，ELISPOT实验证实了这一点。抗IL-10或抗IL-10受体抗体阻断IL-10与IL-10受体的相互作用，消除了MSC CS的抑制能力，表明IL-10在抑制T细胞增殖中起主要作用。添加吲哚胺2,3-双加氧酶（IDO）抑制剂1-甲基-DL-色氨酸（1-MT）也恢复了T细胞的增殖能力。总之，我们证明了MSCs培养上清液中的可溶性介质可以抑制未活化和预活化T细胞的增殖，其中IL-10和IDO发挥重要作用。
