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感染的鼠角膜中的主要组织相容性（MHC）抗原表达和浸润细胞群。通过免疫组织化学，在角膜中疱疹感染后，已证明基质角膜细胞开始表达II类MHC抗原，以及许多T淋巴细胞介导延迟型高敏性（DTH）反应。因此，对这些炎性细胞的有效抑制可能导致角膜碎片最少。在下一项研究中，已将抑制DTH的前腔相关免疫偏差（ACAID）作为针对基质疱疹的新治疗方式研究。与对照组相比，接受了室内注射HSV抗原的小鼠的基质不透明度要少得多。通过使用无胸腺裸鼠的细胞转移实验也证实了这种效果。控制角膜疱疹的其他方法是抑制神经节潜伏期的建立。与其他亚基疫苗不同的候选物不同，能够诱导细胞免疫的截短糖蛋白D（_9D）-Interleukin-2（IL-2），抑制了上皮和基质病变的发展，但不能抑制三叉神经神经节的潜伏期。应重新考虑用于给药的疾病或时间。在另一项研究中，多种近交小鼠被HSV局部接种而无需疤痕。显示每种近交小鼠菌株对局部HSV挑战表现出不同的敏感性。非特异性的局部防御机制可能对此现象是可行的。