Department of Ophthalmology, University of Cologne, 50931 Cologne, Germany.
J Immunol. 2013 Aug 15;191(4):1965-75. doi: 10.4049/jimmunol.1201531. Epub 2013 Jul 12.
Modulation of immune responses is one of the main research aims in transplant immunology. In this study, we investigate the local immunomodulatory properties of soluble CD83 (sCD83) at the graft-host interface using the high-risk corneal transplantation model. In this model, which mimics the inflammatory status and the preexisting vascularization of high-risk patients undergoing corneal transplantation, allogeneic donor corneas are transplanted onto sCD83-treated recipient animals. This model allows the direct and precise application of the immune modulator at the transplantation side. Interestingly, sCD83 was able to prolong graft survival after systemic application as well as after topical application, which is therapeutically more relevant. The therapeutic effect was accompanied by an increase in the frequency of regulatory T cells and was mediated by the immune-regulatory enzyme IDO and TGF-β. In vitro, sCD83 induced long-term IDO expression in both conventional and plasmacytoid dendritic cells via autocrine or paracrine production of TGF-β, a cytokine previously shown to be an essential mediator of IDO-dependent, long-term tolerance. These findings open new treatment avenues for local immune modulation after organ and tissue transplantation.
免疫调节是移植免疫领域的主要研究目标之一。在这项研究中，我们使用高风险角膜移植模型研究了可溶性 CD83（sCD83）在移植物-宿主界面的局部免疫调节特性。在该模型中，模拟了炎症状态和正在接受角膜移植的高风险患者的预先存在的血管化，将同种异体供体角膜移植到 sCD83 处理的受者动物上。该模型允许在移植侧直接和精确地应用免疫调节剂。有趣的是，sCD83 不仅可以通过全身应用，还可以通过局部应用延长移植物的存活期，这在治疗上更相关。治疗效果伴随着调节性 T 细胞频率的增加，并且由免疫调节酶 IDO 和 TGF-β介导。体外，sCD83 通过自分泌或旁分泌产生 TGF-β，诱导常规和浆细胞样树突状细胞中的长期 IDO 表达，TGF-β 先前被证明是 IDO 依赖性长期耐受的必需介质。这些发现为器官和组织移植后局部免疫调节开辟了新的治疗途径。
