Molecular mechanisms of immunosuppressive intraocular microenvironment in corneal transplantation

(1)Tim-3是T细胞功能的调节分子，Gal-9是Tim-3配体。Gal-9在正常小鼠眼和具有存活同种异体移植物的眼的角膜上皮、内皮和虹膜睫状体上组成性表达，Tim-3在浸润同种异体移植物的CD 8 T细胞上表达。接受抗Tim-3 mAb或抗Gal-9 mAb治疗的受者的同种异体移植物存活时间显著短于对照受者。在体外，当角膜用抗Gal-9 mAb预处理时，同种异体反应性T细胞对角膜内皮细胞的破坏增强。Gal-9可能在角膜移植中起免疫抑制作用。在角膜内皮细胞上表达的Gal-9保护它们免受角膜内同种异体反应性T细胞的破坏。(2)ICOS/B7 RP-1信号在角膜移植中具有免疫抑制作用。眼组织上表达的B7 RP-1和T细胞上表达的ICOS可能在眼内相互作用，并在角膜移植物的存活中发挥作用。

(1) Tim-3 is a regulatory molecule for T-cell function, and Gal-9 is a Tim-3 ligand. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 mAb or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Gal-9 may play an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.(2) ICOS/B7RP-1 signaling has an immune suppressive effect in corneal allografts. B7RP-1 expressed on ocular tissue and ICOS expressed on T-cells may interact in the eye and play a role in the survival of the corneal allograft.