Department of General Practice, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Hematology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Bull Exp Biol Med. 2021 Dec;172(2):263-269. doi: 10.1007/s10517-021-05373-3. Epub 2021 Dec 2.
Activation and migration of donor T cells to the host target organs are critical mechanisms in the pathogenesis of graft-versus-host disease (GVHD). The role of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 in the recruitment of T cells during immune or inflammatory response is also well known. For elucidation of the mechanism of the therapeutic effect of human bone marrow derived-mesenchymal stem cells (MSC) in GVHD, we studied the effect of these cells on migration of activated donor T cells through the CCL2-CCR2 axis in vitro. MSC were expanded from donors' bone marrow mononuclear cells. After co-culturing of IL-2-activated T cells with allogeneic MSC at different ratios, the levels of CCL2 in supernatants were measured by ELISA, and CCR2 expression in CD4/CD8 T cells subsets were detected by flow cytometry. The effect of MSC on the migration of activated T cells in the Transwell system was studied in the absence or presence of CCL2. Our results show that CCL2 levels in supernatants of co-cultures were significantly higher than in MSC monoculture and this increase depended on the number of MSC. MSC inhibited proliferation of T cells, but did not change the percentages of CD4 and CD8 T cells subsets. MSC can up-regulate the CCR2 expression in CD8 subsets rather than in CD4 subsets; MSC enhanced migration of IL-2-activated T cells to CCL2 by increasing the expression of CCR2. The data demonstrate that MSC can enhance chemotaxis of cytokine-activated T cells through the CCL2-CCR2 axis in vitro.
供者 T 细胞向宿主靶器官的激活和迁移是移植物抗宿主病（GVHD）发病机制中的关键机制。单核细胞趋化蛋白-1（MCP-1/CCL2）及其受体 CCR2 在免疫或炎症反应期间 T 细胞募集中的作用也众所周知。为了阐明人骨髓来源间充质干细胞（MSC）在 GVHD 中的治疗效果的机制，我们研究了这些细胞通过 CCL2-CCR2 轴在体外对激活的供者 T 细胞迁移的影响。MSC 从供体骨髓单核细胞中扩增。在不同比例的 IL-2 激活的 T 细胞与同种异体 MSC 共培养后，通过 ELISA 测量上清液中的 CCL2 水平，并通过流式细胞术检测 CD4/CD8 T 细胞亚群中的 CCR2 表达。在不存在或存在 CCL2 的情况下，研究了 MSC 对活化 T 细胞在 Transwell 系统中的迁移的影响。我们的结果表明，共培养上清液中的 CCL2 水平明显高于 MSC 单核培养物，并且这种增加取决于 MSC 的数量。MSC 抑制 T 细胞的增殖，但不改变 CD4 和 CD8 T 细胞亚群的百分比。MSC 可以上调 CD8 亚群中的 CCR2 表达，而不是 CD4 亚群中的 CCR2 表达；MSC 通过增加 CCR2 的表达增强了 IL-2 激活的 T 细胞向 CCL2 的迁移。数据表明，MSC 可以通过体外的 CCL2-CCR2 轴增强细胞因子激活的 T 细胞的趋化性。
