Hori J, Streilein J W
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Invest Ophthalmol Vis Sci. 2001 Mar;42(3):720-6.
To determine whether epithelium-deprived corneal allografts covered with syngeneic epithelium display immune privilege in orthotopic transplantation and whether syngeneic epithelium containing antigen-presenting cells nullifies this effect.
Epithelium-deprived allogeneic corneas (C57BL/6) and epithelium-deprived allogeneic corneas reconstituted with syngeneic (BALB/c) epithelium (containing or deprived of Langerhans' cells) were transplanted orthotopically into normal eyes of BALB/c mice. Graft survival was assessed clinically and evaluated histologically.
Epithelium-deprived corneal grafts survived in syngeneic recipients but were swiftly rejected in allogeneic recipients. These allografts incited intense stromal inflammation and neovascularization. Epithelium-deprived allografts that were resurfaced in vivo by syngeneic epithelium derived from immune-incompetent SCID mice also underwent intense acute rejection when placed in normal eyes of BALB/c mice. The epithelium of in vivo resurfaced grafts was replete with Langerhans' cells. By contrast, most of the epithelium-deprived allografts reconstituted in vitro with fresh, normal BALB/c corneal epithelium survived indefinitely when placed in eyes of BALB/c mice. Similar grafts reconstituted with BALB/c epithelium containing Langerhans' cells were swiftly rejected.
Replacement of donor epithelium with Langerhans' cell-deficient syngeneic epithelium protects orthotopic allogeneic cornea grafts (stroma plus endothelium) from immune-mediated rejection. The presence of an intact, histocompatible layer of corneal epithelium has two important effects on orthotopic corneal allografts: It suppresses nonspecific inflammation and neovascularization within the graft, and it blunts the alloimmunogenicity of the histoincompatible stroma and endothelium.
确定覆盖有同基因上皮的去上皮角膜同种异体移植在原位移植中是否表现出免疫赦免,以及含有抗原呈递细胞的同基因上皮是否会消除这种效应。
将去上皮同种异体角膜(C57BL/6)以及用同基因(BALB/c)上皮(含或不含朗格汉斯细胞)重建的去上皮同种异体角膜原位移植到BALB/c小鼠的正常眼中。临床评估移植物存活情况,并进行组织学评估。
去上皮角膜移植物在同基因受体中存活,但在异基因受体中迅速被排斥。这些同种异体移植物引发强烈的基质炎症和新生血管形成。由免疫缺陷的SCID小鼠来源的同基因上皮在体内重新覆盖的去上皮同种异体移植物,当置于BALB/c小鼠的正常眼中时,也经历了强烈的急性排斥反应。体内重新覆盖的移植物上皮富含朗格汉斯细胞。相比之下,用新鲜的正常BALB/c角膜上皮在体外重建的大多数去上皮同种异体移植物,当置于BALB/c小鼠眼中时可无限期存活。用含有朗格汉斯细胞的BALB/c上皮重建的类似移植物被迅速排斥。
用缺乏朗格汉斯细胞的同基因上皮替代供体上皮可保护原位同种异体角膜移植物(基质加内皮)免受免疫介导的排斥。完整的、组织相容性的角膜上皮层对原位角膜同种异体移植物有两个重要作用:它抑制移植物内的非特异性炎症和新生血管形成,并减弱组织不相容的基质和内皮的同种免疫原性。