Larkin D F, Calder V L, Lightman S L
Department of Clinical Science, Institute of Ophthalmology, London, UK.
Clin Exp Immunol. 1997 Feb;107(2):381-91. doi: 10.1111/j.1365-2249.1997.279-ce1171.x.
In a rat model of corneal transplantation, Fischer 344 (RT1(lv1)) rats received orthotopic corneal isografts or Wistar-Furth (RT1(u)) donor allografts. Rejection was observed in 25 of 26 allograft recipients, at a median time of 18 days, with all isografts surviving > 100 days. Flow cytometric analysis of aqueous humour identified cellular infiltration of the aqueous at the time of allograft rejection, in contrast to the acellular aqueous found in isografts at corresponding times following transplantation. A higher proportion of CD8+ than CD4+ cells was found at days 1-3 following rejection, whereas there was a higher proportion of CD4+ cells at days 5-8. No changes in peripheral blood T cell subsets were found at the time of rejection. Immunohistochemical analysis of cells infiltrating recipient iris and grafted cornea undertaken at days 1-2, 4 and 7-10 following onset of rejection, demonstrated inflammatory cells in the graft epithelium, stroma and aggregated on the endothelium. Large numbers of macrophages, T cells (CD4+ > CD8+ at all time points), natural killer (NK) cells and neutrophils were detected in graft tissue at days 1-2 and 4, diminishing after that time. Most infiltrating cells expressed MHC class II antigen, and a smaller number expressed IL-2R. Expression of the co-stimulatory marker B7 was identified in a few cells at day 4 in the region of the graft-host wound. The immune response in graft rejection was characterized at day 4 also by expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells of iris and corneal vessels, demonstration of interferon-gamma on mononuclear cells in the peripheral (recipient) cornea, and tumour necrosis factor-alpha on aggregated mononuclear cells on the graft, but not recipient, endothelium. Only sparse cellular infiltrates were found in isograft controls, with inflammation located at the graft-host wound. These findings suggest that inflammatory cells reach a corneal allograft by two routes--from vessels in the peripheral recipient cornea, and from vessels in the recipient iris via the aqueous humour. Different aqueous and intragraft T cell subset proportions were seen early in rejection, although a preponderance of CD4+ cells was found in both aqueous and graft at later times.
在角膜移植大鼠模型中，Fischer 344（RT1(lv1)）大鼠接受原位角膜同基因移植或Wistar-Furth（RT1(u)）供体的同种异体移植。26只同种异体移植受体中有25只出现排斥反应，中位时间为18天，所有同基因移植均存活超过100天。房水的流式细胞术分析显示，同种异体移植排斥时房水有细胞浸润，而移植后相应时间同基因移植的房水无细胞。排斥反应后第1 - 3天，CD8 +细胞比例高于CD4 +细胞，而第5 - 8天CD4 +细胞比例更高。排斥反应时外周血T细胞亚群无变化。在排斥反应开始后第1 - 2天、4天以及7 - 10天对受体虹膜和移植角膜中的浸润细胞进行免疫组织化学分析，结果显示移植上皮、基质中有炎性细胞，并在内皮上聚集。在第1 - 2天和4天，移植组织中检测到大量巨噬细胞、T细胞（所有时间点CD4 +均多于CD8 +）、自然杀伤（NK）细胞和中性粒细胞，之后数量减少。大多数浸润细胞表达MHC II类抗原，少数表达IL - 2R。在移植 - 宿主伤口区域，第4天少数细胞中鉴定出共刺激标志物B7的表达。移植排斥反应第4天的免疫反应特征还包括虹膜和角膜血管内皮细胞上细胞间黏附分子 - 1（ICAM - 1）的表达、外周（受体）角膜单核细胞上干扰素 - γ的表达以及移植而非受体内皮上聚集单核细胞上肿瘤坏死因子 - α的表达。同基因移植对照组仅发现稀疏的细胞浸润，炎症位于移植 - 宿主伤口处。这些发现表明，炎性细胞通过两条途径到达角膜同种异体移植部位——从外周受体角膜的血管以及从受体虹膜的血管经房水到达。排斥反应早期房水和移植内T细胞亚群比例不同，尽管后期房水和移植内均以CD4 +细胞为主。
