Study of cellular immune responses against herpetic keratitis

针对疱疹性角膜炎的细胞免疫反应研究

基本信息

批准号：
02670786
负责人：
OHASHI Yuichi
金额：
$ 1.6万
依托单位：
Ehime University (1992)Osaka University (1990-1991)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

We first analyzed major histocompatibility (MHC) antigen expressionand infiltrated cell populations in HSV-infected murine corneas. By immunohistochemistry, stromal keratocytes have been shown to begin to express class II MHC antigens following herpetic infection in the cornea, along with numerous T lymphocytes mediating delayed type hypersensitivity (DTH) reactions. Thus, effective suppression of these inflammatory cells may lead to minimal corneal scarring. In the next study, anterior chamber-associated immune deviation (ACAID) which has been shown to suppress DTH was investigated as a new therapeutic modality against stromal herpes. The mice that had received intracameral injection of HSV-antigens developed much less stromal opacity as compared with controls. This effect was also confirmed by cell transfer experiments using athymic nude mice.Another way to control corneal herpes is to inhibit the establishment of ganglionic latency. A truncated-glycoprotein D (_9D)-interleukin-2 (IL-2),which is capable of inducing cellular immunity unlike other subunit vaccine candidates, suppressed the development of epithelial as well as stromal lesions but could not inhibit the trigeminal ganglionic latency. The dosis or timing for administration should be reconsidered.In another study, a variety of inbred mice were topically inoculated with HSV without scarification. Each inbred mouse strain was shown to exhibit different susceptibility to topical HSV challenge. Non-specific, local defense mechanisms may be operative for this phenomenon.

我们首先分析了 HSV 感染的小鼠角膜中主要组织相容性 (MHC) 抗原的表达和浸润细胞群。通过免疫组织化学，基质角膜细胞已被证明在角膜疱疹感染后开始表达 II 类 MHC 抗原，同时还有大量介导迟发型超敏反应 (DTH) 反应的 T 淋巴细胞。因此，有效抑制这些炎症细胞可能会导致角膜疤痕最小化。在下一项研究中，前房相关免疫偏差 (ACAID) 已被证明可以抑制 DTH，作为一种针对间质疱疹的新治疗方式进行了研究。与对照组相比，接受前房内注射 HSV 抗原的小鼠的基质混浊程度要低得多。使用无胸腺裸鼠的细胞转移实验也证实了这种效果。控制角膜疱疹的另一种方法是抑制神经节潜伏期的建立。与其他候选亚单位疫苗不同，截短糖蛋白 D (_9D)-白介素-2 (IL-2) 能够诱导细胞免疫，抑制上皮和间质病变的发展，但不能抑制三叉神经节潜伏期。应重新考虑给药剂量或时间。在另一项研究中，多种近交系小鼠局部接种 HSV，但未进行划痕。每种近交系小鼠品系对局部 HSV 攻击表现出不同的敏感性。非特异性的局部防御机制可能对这种现象起作用。