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The Roles of T Cells in the Pathogenesis of Ocular Viral Infections

T 细胞在眼部病毒感染发病机制中的作用

基本信息

批准号：
09470379
负责人：
INOUE Yoshitsugu
金额：
$ 1.54万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470379/
关键词：
herpetic keratitis T cell herpes simplex virus cytokine DNA vaccine glycoprotein D Th1 cell Th2 cell 単純ヘルペスウィルスインターフェロンα インターロイキン-4 インターフェロンγ インターロイキン4

项目摘要

1. Human neutrophil chemotaxis induced by herpes simplex virus (HSV) infectionUsing in-vitro system with human corneal epithelial cells immortalized with SV-40, human corneal stromal cells, human neutrophils, and Boyden chamber, human neutrophil chemotaxis was found to be induced by HSV-infected corneal epithelial cells and stromal cells after infection of HSV via interleukin-8.2. Cytokine production from human peripheral blood T lymphocytes of herpetic keratitis patients(1) T lymphocytes and antigen-presenting cells primed with UV-inactivated HSV and irradiated with γ-ray, culture media were collected, and the amounts of cytokines were measured with ELISA.(2) T lymphocytes of herpetic keratitis patients produced Th1 cytokines such as IFN-γ and IL-2, but not Th2 cytokines (actually minimal level of IL-10 and under-detection level of IL-4)(3) Patients with herpetic recurrences of stromal type within 1 year produced higher level of Th1 cytokines and indicated significantly higher ratio o … More f IFN-γ/IL-10 and IL-2/IL-10 than those with herpetic recurrences of epithelial type within 1 year.3. The efficacy of herpes vaccine in murine herpetic keratitis modelTo investigate the utility of immune therapy with herpes vaccine, we constructed chimera-protein consisted of HSV glycoprotein-D and human IL-2, and study its efficacy using primary corneal HSV infection model in mice.(1) Systemic and local (subconjunctival) administration of gD-IL-2 protein inhibited the development of stromal type of herpetic keratitis.(2) Subconjunctival injection of gD-IL-2 DNA induced humoral and cellular immunity against HSV.(3) Subconjunctival injection of gD-IL-2 DNA inhibited the development of stromal type of herpetic keratitis.(4) Subconjunctival injection of gD-IL-2 DNA suppressed viral proliferation in eyes, trigeminal ganglia, and brains.4. Immunohistochemical study in murine herpetic keratitis modelUsing murine herpetic keratitis model, cytokines, adhesion molecules, infiltrated cells, and major histocompatibility antigens in cornea and local lymph nodes were immunohistochemically studied, and dense localization of Th1 cytokines and γδ-T cells was ascertained. Less

1.单纯疱疹病毒(HSV)感染诱导的人中性粒细胞趋化性使用SV-40永生化人角膜上皮细胞、人角膜基质细胞、人中性粒细胞和Boyden小室的体外系统，发现HSV感染后，HSV感染的角膜上皮细胞和基质细胞可诱导人中性粒细胞趋化性白介素-8.2。带状疱疹性角膜炎患者外周血T淋巴细胞产生细胞因子(1)用UV灭活HSV引发并用γ射线照射的T淋巴细胞和抗原呈递细胞，收集培养基，并用ELISA测定细胞因子的量。(2)带状疱疹性角膜炎患者T淋巴细胞产生Th1 IFN-γ 和 IL-2 等细胞因子，但不是 Th2 细胞因子（实际上 IL-10 水平最低，IL-4 水平检测不足）(3) 1 年内间质型疱疹复发患者产生更高水平的 Th1 细胞因子，并且 IFN-γ/IL-10 和 IL-2/IL-10 比值显着高于 1 年内间质型疱疹复发患者。 1年内上皮型。3．疱疹疫苗在小鼠疱疹性角膜炎模型中的功效为了研究疱疹疫苗免疫治疗的效用，我们构建了由HSV糖蛋白-D和人IL-2组成的嵌合蛋白，并利用小鼠原发性角膜HSV感染模型研究其功效。（1）全身和局部（结膜下）施用gD-IL-2蛋白抑制了疱疹病毒的发展。 (2) 结膜下注射 gD-IL-2 DNA 诱导针对 HSV 的体液和细胞免疫。(3) 结膜下注射 gD-IL-2 DNA 抑制基质型疱疹性角膜炎的发展。(4) 结膜下注射 gD-IL-2 DNA 抑制眼睛、三叉神经中的病毒增殖神经节和大脑.4。小鼠疱疹性角膜炎模型的免疫组织化学研究采用小鼠疱疹性角膜炎模型，对角膜和局部淋巴结中的细胞因子、粘附分子、浸润细胞和主要组织相容性抗原进行免疫组织化学研究，并确定Th1细胞因子和γδ-T细胞的密集定位。较少的