Molecular mechanisms of immune privilege of corneal transplantation

程序性死亡-1 （PD-1）共刺激通路已被证明在免疫应答和外周耐受的调节中发挥作用。我们研究了这一途径在小鼠角膜异体移植建立免疫特权状态中的作用。B7-H1在角膜、虹膜-睫状体和视网膜中组成性表达，而B7-DC和PD-1不组成性表达。同种异体角膜移植后，PD-1^+ CD4^+ T细胞浸润并粘附于B7-H1^+角膜内皮。阻断PD-1或B7-H1，而不阻断B7-DC，可加速角膜异体移植排斥反应。在表达b7 - h1的角膜异体移植物中，观察到浸润的PD-1^+ CD4^+或CD8^+ T细胞凋亡，之后出现异体移植接受。B7-H1阻断可抑制PD-1 +T细胞的凋亡，导致同种异体移植排斥反应。在体外，当角膜预处理抗b7 - h1抗体时，同种异体反应性T细胞对角膜内皮细胞的破坏增强。这是首次证明B7-H1的组成表达在角膜移植存活中起关键作用。在角膜内皮细胞上表达的B7-H1通过诱导角膜内效应T细胞的凋亡来维持对异体角膜移植物的长期接受。

The programmed death-1 (PD-1) costimulatory pathway has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in establishing an immune privilege status of corneal allografts in mice. B7-H1, but not B7-DC or PD-1, was expressed constitutively in the eye, i.e., cornea, iris-ciliary body and retina. After corneal allografting, PD-1^+ CD4^+ T cells infiltrated and adhered with B7-H1^+ corneal endothelium. Blockade of PD-1 or B7-H1, but not B7-DC, led to accelerated corneal allograft rejection. In B7-H1-expressing corneal allografts, apoptosis of the infiltrating PD-1^+ CD4^+ or CD8^+ T cells was observed, after which there was allograft acceptance. In contrast, B7-H1 blockade suppressed apoptosis of infiltrating PD-1^+T cells, which led to allograft rejection. In vitro, destruction of corneal endothelial cells by alloreactive T cells was enhanced when the cornea was pre-treated with anti-B7-H1 antibody. This is the first demonstration that the constitutive expression of B7-H1 plays a critical role in corneal allograft survival. B7-H1 expressed on corneal endothelial cells maintains long-term acceptance of the corneal allografts by inducing apoptosis of effector T cells within the cornea.