Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells.
Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells.
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DOI：
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发表时间：
2006
期刊：
影响因子：
5.2
通讯作者：
M. Krampera;L. Cosmi;R. Angeli;A. Pasini;F. Liotta;A. Andreini;V. Santarlasci;B. Mazzinghi;G. P
中科院分区：
文献类型：
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作者：
M. Krampera;L. Cosmi;R. Angeli;A. Pasini;F. Liotta;A. Andreini;V. Santarlasci;B. Mazzinghi;G. P
间充质干细胞（MSC）抑制HLA无关的T淋巴细胞对同种异体刺激的增殖，但负责这种活动的机制尚未完全了解。我们在这里显示，MSC抑制CD 4+和CD 8 + T淋巴细胞以及自然杀伤（NK）细胞的增殖，而它们对B淋巴细胞的增殖没有影响。MSC的抗增殖作用与对细胞活化标志物的表达、细胞凋亡的诱导或T调节细胞活性的模拟/增强的任何作用无关。MSC的抑制活性不是接触依赖性的，并且需要由活化的T细胞和NK细胞产生的干扰素（IFN）-γ的存在。因此，即使活化的B细胞在外源性添加的IFN-γ存在下也变得对MSC的抑制活性敏感。IFN-γ的抑制作用与其刺激MSC产生吲哚胺2，3-双加氧酶活性的能力有关，这反过来又抑制了活化的T或NK细胞的增殖。这些发现表明，与MSC移植物体内共输注诱导的对移植物抗宿主病的有益作用可能是由于T细胞衍生的IFN-γ激活了MSC的免疫调节特性。
Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-gamma produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-gamma. The suppressive effect of IFN-gamma was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell- derived IFN-gamma.