角膜移植免疫排斥反应细胞疗法的研究进展

Recent advances of cellular therapy for corneal graft rejection

角膜移植术后免疫排斥反应是导致手术失败的主要原因，而临床上常用的免疫抑制剂存在着许多不良反应。细胞治疗效果确切，不良反应少，已成为新的研究热点。大量研究表明，在诱导、维持机体免疫耐受和免疫应答稳态方面具有重要作用的调节性T细胞能直接参与角膜移植术后免疫耐受的形成。近年来，树突状细胞被发现在免疫系统中扮演着双重角色，除作为抗原递呈细胞诱发免疫反应外，不成熟或表达抑制性细胞因子的树突状细胞还可诱导免疫耐受。体内外研究表明，间充质干细胞是一种具有多向分化潜能的非造血基质细胞，可通过对免疫细胞的影响，诱导抗炎效应和／或免疫耐受状态，有效抑制器官移植排斥反应。而作为继Tregs之后的又一热点细胞，髓源性抑制细胞能由多种途径抑制效应性T细胞增生，减少细胞因子的分泌，促进T细胞凋亡，抑制B细胞、NK细胞和巨噬细胞等的活动，甚至能诱导Tregs的产生，在抑制自身免疫性疾病和器官移植排斥中起着重要的作用。本文就以上4种细胞的免疫特点及其在角膜移植排斥反应治疗方面的研究进展进行综述。

Immune rejection is the leading cause of graft failure, and the main way for preventing corneal graft rejection is the application of immunosuppressive drugs. However,in the recent years, cellular therapy has been a new research hotspot for its targeted effect and fewer side effect. A lot of researches showed that Treg ceils which are important in inducing and maintaining immunological tolerance could directly induce immune tolerance in corneal transplantation. In recent years, dendritic ceils also are found to have a dual role in the immune system, except as antigen presenting cells to induce immune response. Immature or immunosuppressive eytokine-expressing dendritic cells can induce immune tolerance. Mesenehymal stem cells which have multiple differentiation potential can exert anti-inflammatory effects on immune cells and effectively inhibit organ transplant rejection in vitro and in vivo. As another hotspot besides Tregs, myeloid-derived suppressor cells can inhibit the proliferation of a broad range of immune cells （T and B cells, NK cells, and macrophages） , induce T cells apoptosis, and even induce Tregs. This review provides an update of these four kinds of cells on their effects and developments in cellular therapy for experimental corneal graft rejection.