Hendricks R L
Department of Ophthalmology, University of Illinois at Chicago 60612, USA.
Cornea. 1997 Sep;16(5):503-6.
To review recent progress in understanding the mechanisms of herpes simplex virus 1 (HSV-1)-induced immunopathology in the cornea, as revealed by studies in a mouse model.
The corneas of A/J mice were infected with 5 x 10(4) plaque-forming units (PFU) of the RE strain of HSV-1, and the development of inflammation was assessed by slitlamp, histologic, or immunohistochemical examination. The immunopathologic mechanisms were then defined by observing the effect of in vivo depletion of corneal Langerhans' cells, or T-lymphocyte subpopulations, or in vivo neutralization of cytokines on adhesion molecule expression or leukocytic infiltration of the infected cornea.
After corneal infection, 60-70% of mice develop corneal opacity due to leukocytic infiltration, neovascularization, and edema. Polymorphonuclear neutrophils (PMN) represent 90% of the infiltrating cells, with numerous CD4+, but few CD8+, T cells present. Depleting CD4+ T cells of Langerhans' cells prevents inflammation from developing. Neutralizing interleukin-2 (IL-2) or interferon gamma (IFN-gamma) can prevent inflammation or cause a remission of existing disease. IFN-gamma neutralization causes a rapid block of PMN extravasation from the blood in association with reduced platelet endothelial cell adhesion molecule 1 (PECAM-1) expression on the corneal vascular endothelium. IL-2 neutralization results in decreased IFN-gamma production, reduced chemotaxis, and loss of PMN viability in the infected cornea.
Herpes stromal keratitis is a CD4+ T cell-dependent inflammatory process in which PMN infiltration and destruction of the cornea are regulated, at least in part, by the T-helper type 1 (Th1) cytokines IL-2 and IFN-gamma.
通过在小鼠模型中的研究,综述在理解单纯疱疹病毒1型(HSV-1)诱导的角膜免疫病理学机制方面的最新进展。
用5×10⁴空斑形成单位(PFU)的HSV-1 RE株感染A/J小鼠的角膜,通过裂隙灯、组织学或免疫组织化学检查评估炎症的发展。然后通过观察体内去除角膜朗格汉斯细胞、T淋巴细胞亚群或体内中和细胞因子对感染角膜黏附分子表达或白细胞浸润的影响来确定免疫病理机制。
角膜感染后,60%-70%的小鼠因白细胞浸润、新生血管形成和水肿而出现角膜混浊。多形核中性粒细胞(PMN)占浸润细胞的90%,有大量CD4⁺但很少CD8⁺ T细胞。去除朗格汉斯细胞的CD4⁺ T细胞可防止炎症发展。中和白细胞介素-2(IL-2)或干扰素γ(IFN-γ)可预防炎症或使现有疾病缓解。IFN-γ中和导致PMN从血液中快速渗出受阻,同时角膜血管内皮上血小板内皮细胞黏附分子1(PECAM-1)表达减少。IL-2中和导致感染角膜中IFN-γ产生减少、趋化性降低和PMN活力丧失。
疱疹性基质性角膜炎是一种CD4⁺ T细胞依赖性炎症过程,其中PMN浸润和角膜破坏至少部分受1型辅助性T细胞(Th1)细胞因子IL-2和IFN-γ调节。