Tianjin Medical University Eye Hospital and Eye Institute, 251 Fu Kang Road, Tianjin, China.
Int Immunopharmacol. 2013 Jan;15(1):114-20. doi: 10.1016/j.intimp.2012.11.007. Epub 2012 Nov 21.
Introduction of antigen into anterior chamber (AC) induces a deviant immune response termed anterior chamber-associated immune deviation (ACAID) that protects the eye from inflammatory destruction consequent to a systemic immune response. Mesenchymal stem cells (MSCs) can modulate a variety of immune responses. However, the effects of systemic administration of MSCs on ACAID have not been explored. In this study, C57BL/6 mice were inoculated with ovalbumin in the AC to induce ACAID, control group received AC injection of solvent alone. Immediately after the AC injection, the mice were injected through the tail vein with human Umbilical Cord-derived MSCs (hUC-MSC) or phosphate buffer saline. All animals were subcutaneously immunized with ovalbumin one week later. Delayed-type hypersensitivity assay was performed another week following immunization. The splenic monocytes were then isolated, cultured and stimulated with ovalbumin. Levels of IL-10, TGF-β, and IFN-γ in culture media were measured by ELISA. The frequencies of CD4(+)CD25(+)Foxp3(+) and CD8(+)Foxp3(+) regulatory T cells (Tregs) were determined by flow cytometry. The results showed that the AC inoculation of ovalbumin induced significantly less ear swelling than controls, confirming the establishment of ACAID. MSCs potentiated IL-10 and TGF-β production, further suppressed IFN-γ secretion from splenic monocytes in ACAID mice, and enhanced expansion of CD4(+)CD25(+)Foxp3(+) and CD8(+)Foxp3(+) Tregs isolated from the spleen of ACAID mice. Therefore, our study, for the first time, provides clear evidence that systemic administration of MSCs augments cytokine production and Treg expansion from ACAID spleens, which may contribute to promotion and maintenance of ACAID.
介绍抗原到前房（AC）引起一种异常的免疫反应，称为前房相关免疫偏离（ACAID），它可以保护眼睛免受炎症破坏继发于全身免疫反应。间充质干细胞（MSCs）可以调节各种免疫反应。然而，全身给予 MSCs 对 ACAID 的影响尚未被探索。在这项研究中，C57BL/6 小鼠在前房内接种卵清蛋白诱导 ACAID，对照组接受前房溶剂注射。在前房注射后，立即通过尾静脉给予人脐带源间充质干细胞（hUC-MSC）或磷酸盐缓冲盐水。所有动物均于一周后经皮下免疫卵清蛋白。免疫后一周进行迟发型超敏反应试验。然后分离、培养和刺激脾单核细胞，并与卵清蛋白共培养。通过 ELISA 测定培养上清液中 IL-10、TGF-β和 IFN-γ的水平。通过流式细胞术测定 CD4(+)CD25(+)Foxp3(+)和 CD8(+)Foxp3(+)调节性 T 细胞（Tregs）的频率。结果显示，卵清蛋白前房接种诱导的耳肿胀明显小于对照组，证实了 ACAID 的建立。MSCs 增强了 IL-10 和 TGF-β的产生，进一步抑制了 ACAID 小鼠脾单核细胞 IFN-γ的分泌，并增强了从 ACAID 小鼠脾分离的 CD4(+)CD25(+)Foxp3(+)和 CD8(+)Foxp3(+)Tregs 的扩增。因此，本研究首次提供了明确的证据，表明全身给予 MSCs 增强了 ACAID 脾脏细胞因子的产生和 Treg 的扩增，这可能有助于 ACAID 的促进和维持。
