Umbilical Cord-Derived Mesenchymal Stromal Cells Modulate Monocyte Function to Suppress T Cell Proliferation
Umbilical Cord-Derived Mesenchymal Stromal Cells Modulate Monocyte Function to Suppress T Cell Proliferation
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DOI：
10.4049/jimmunol.1002239
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发表时间：
2010-12-01
影响因子：
4.4
通讯作者：
Navarrete, Cristina V.
中科院分区：
文献类型：
--
作者：
Cutler, Antony J.;Limbani, Vasanti;Navarrete, Cristina V.
间充质基质细胞（MSC）可来源于多种组织，人脐带（UC）提供了丰富的和非侵入性的来源。人UC-MSC与从骨髓和脐带血获得的MSC具有相似的体外免疫抑制特性。然而，MSC用于控制免疫应答的机制和细胞相互作用仍有待充分阐明。在本文中，我们报告说，抑制丝裂原诱导的T细胞增殖的人UC，骨髓，脐带血间充质干细胞需要单核细胞。从人成人PBMCs（PBMNCs）中去除单核细胞而不是B细胞降低了MSC对T细胞增殖的免疫抑制作用。当PBMC或同种异体抗原激活的PBMC与UC-MSC一起培养时，单核细胞上的许多细胞表面分子发生快速调节。吲哚美辛治疗显著抑制UC-MSC抑制T细胞增殖的能力，表明PGE的重要作用（2）。在随后的T细胞增殖试验中，从UC-MSC共培养物中纯化的单核细胞的辅助细胞和同种异体刺激功能显著降低，这种作用部分由UC-MSC PGE（2）产生介导，并由PBMNC同种异体激活增强。因此，我们确定单核细胞作为一个重要的中介，通过UC-MSC介导其对T细胞增殖的抑制作用。免疫学杂志，2010，185：6617-6623。
Mesenchymal stromal cells (MSCs) may be derived from a variety of tissues, with human umbilical cord (UC) providing an abundant and noninvasive source. Human UC-MSCs share similar in vitro immunosuppressive properties as MSCs obtained from bone marrow and cord blood. However, the mechanisms and cellular interactions used by MSCs to control immune responses remain to be fully elucidated. In this paper, we report that suppression of mitogen-induced T cell proliferation by human UC-, bone marrow-, and cord blood-MSCs required monocytes. Removal of monocytes but not B cells from human adult PBMCs (PBMNCs) reduced the immunosuppressive effects of MSCs on T cell proliferation. There was rapid modulation of a number of cell surface molecules on monocytes when PBMCs or alloantigen-activated PBMNCs were cultured with UC-MSCs. Indomethacin treatment significantly inhibited the ability of UC-MSCs to suppress T cell proliferation, indicating an important role for PGE(2). Monocytes purified from UC-MSC coculture had significantly reduced accessory cell and allostimulatory function when tested in subsequent T cell proliferation assays, an effect mediated in part by UC-MSC PGE(2) production and enhanced by PBMNC alloactivation. Therefore, we identify monocytes as an essential intermediary through which UC-MSCs mediate their suppressive effects on T cell proliferation. The Journal of Immunology, 2010, 185: 6617-6623.