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的配体。Gal-9在正常小鼠眼和存活同种异体移植眼的角膜上皮、内皮和虹膜睫状体表达，TIM-3在CD8T细胞上表达。抗TIM-3单抗和抗Gal-9单抗治疗的受者移植肾存活时间明显短于对照组。在体外，抗Gal-9单抗可增强同种反应性T细胞对角膜内皮细胞的破坏作用。GAL-9可能在同种异体角膜移植中起免疫抑制作用。表达于角膜内皮细胞上的GAL-9保护其免受角膜内同种反应性T细胞的破坏。(2)ICOS/B7RP-1信号在角膜移植中具有免疫抑制作用。眼组织上表达的B7RP-1和T细胞上表达的ICOS可能在眼内相互作用，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.