Tianjin Medical University Eye Center, Tianjin, China.
Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3143-52. doi: 10.1167/iovs.10-6334.
The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP).
The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected.
MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells.
These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
作者研究了大鼠间视网膜结合蛋白（IRBP）肽 1169-1191 诱导的实验性自身免疫性葡萄膜炎（EAU）中大鼠间充质干细胞（MSCs）的治疗作用。
作者将同基因（源自 Lewis 大鼠）或异基因（源自 Wistar 大鼠）MSCs 静脉注射入 IRBP 诱导的 EAU Lewis 大鼠体内，在疾病发病前（与免疫同时，预防方案）或疾病发病后不同时间点（治疗方案）进行注射。评估经 MSC 处理的大鼠对 IRBP 1169-1191 的 T 细胞反应，测量淋巴细胞产生的 Th1/Th2/Th17 细胞因子，并检测 CD4+CD25+调节性 T 细胞（Treg）。
疾病发病前给予 MSC 治疗不仅显著降低了 EAU 的严重程度，还延迟了疾病的发病。疾病发病后和疾病高峰期给予 MSC 治疗也是有效的，但在疾病稳定期则无效。所有治疗的临床疗效与细胞浸润减少以及葡萄膜和视网膜损伤减轻一致。经 MSC 处理的大鼠对 IRBP 1169-1191 的 T 细胞反应受到抑制。MSCs 显著降低了 EAU 大鼠 T 淋巴细胞 IFN-γ和 IL-17 的产生，增加了 IL-10 的产生，无论是在体内还是在体外。同种异体和同基因 MSCs 在临床疗效、T 细胞增殖和细胞因子分泌方面均表现出相似的免疫抑制潜力，并且 MSC 治疗可上调 Treg 细胞。
这些数据表明，MSCs 的免疫调节特性通过对系统性自身免疫的全面调节，有效地干扰了 EAU 过程中的自身免疫攻击。
