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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.

我们首先分析了主要组织相容性（MHC）抗原表达和HSV感染的小鼠角膜浸润细胞群。通过免疫组织化学，基质角膜细胞已被证明开始表达II类MHC抗原疱疹感染后，在角膜，沿着大量的T淋巴细胞介导迟发型超敏反应（DTH）。因此，有效抑制这些炎性细胞可导致最小的角膜瘢痕形成。在接下来的研究中，前房相关免疫偏离（ACAID）已被证明可以抑制DTH，作为一种新的治疗方式对基质疱疹进行了研究。与对照组相比，前房内注射HSV抗原的小鼠发生了更少的基质混浊。这种作用也被无胸腺裸鼠的细胞移植实验所证实。另一种控制角膜疱疹的方法是抑制神经节潜伏期的建立。截短的糖蛋白D（_9D）-白细胞介素-2（IL-2）能够诱导细胞免疫，与其他亚单位疫苗候选者不同，它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。在另一项研究中，用HSV局部接种各种近交系小鼠而不划痕。显示每种近交系小鼠品系对局部HSV攻击表现出不同的易感性。非特异性的局部防御机制可能对这种现象起作用。