IMMUNOLOGY AND GENETICS OF HERPES SIMPLEX KERATITIS

单纯疱疹性角膜炎的免疫学和遗传学

• 批准号: 3261919
• 负责人: CHARLES STEPHEN FOSTER
• 金额: $ 20.6万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3261919
• 关键词: Alphaherpesvirinae; T cell receptor; T lymphocyte; alleles; antiviral antibody; cell mediated cytotoxicity; cellular pathology; corneal epithelium; corneal stroma; genetic strain; hybridomas; immunoglobulin genes; immunoglobulin idiotypes; immunopathology; immunoregulation; keratitis; laboratory mouse; linkage mapping; minor histocompatibility loci; molecular pathology; monoclonal antibody

Herpes stromal keratitis (HSK) is a devastating problem for which no completely satisfactory therapy exists. The immunopathogenesis of HSK is incompletely understood. We have produced and studied a murine model of HSK and have shown a strong influence of the gene in or closely linked to the Igh immunoglobulin allotype loci on Chromosome 12 on the immune/inflammatory response to herpes encounter n the cornea. The interplay between lymphocyte-mediated and antibody-mediated responses in protection from versus production of inflammatory corneal destruction is complicated, but results from our studies suggest that the critical determinants in mediating the balance between protection as opposed to pathology development revolve around immunoregulatory control which derives from products encoded by the Igh-1 and closely linked genes on Chromosome 12. Our studies lead us to the hypothesis that antibody idiotypic domain differences between anti-herpes simplex antibody responses and/or differences in HSV-specific T cell receptor repertoires in Igh-1 disparate congenic mice result in differences in cell responses, cell recruitment, and development of clinically obvious pathology in the form of keratopathy. We intend to further analyze the phenomenon of Igh- 1 restriction of HSV-mediated ocular pathology to an analysis of the Igh- governed selection of HSV-specific T cell receptor repertoires. We believe that understanding, on a molecular level, the details of immunoregulatory control of the immune response to herpes simplex virus as it is seen in the eye will provide better insight into more specific therapeutic modulation of inappropriate inflammatory responses to HSV.

疱疹间质角膜炎(HSK)是一个毁灭性的问题，没有 目前存在完全令人满意的治疗方法。单纯疱疹病毒感染的免疫发病机制是 不完全理解。我们已经制作并研究了一种小鼠模型 并已显示出与HSK基因有很强的影响力或密切连锁 12号染色体上的IgH免疫球蛋白等位基因座 对疱疹的免疫/炎症反应在角膜中遇到。这个 淋巴细胞和抗体介导的免疫应答之间的相互作用 对炎症性角膜破坏的保护与产生 很复杂，但我们的研究结果表明，关键的 调解保护与保护之间的平衡的决定因素 病理学的发展围绕着免疫调节控制，它 来源于IgH-1编码的产物和紧密连锁的基因 12号染色体。我们的研究引导我们假设抗体 抗单纯疱疹病毒抗体的独特型结构域差异 单纯疱疹病毒特异性T细胞受体谱系的反应和/或差异 在IgH-1不同的同源基因小鼠中导致细胞反应的差异， 细胞募集和临床上明显的病理发展 一种角膜病。我们打算进一步分析这一现象-- 1单纯疱疹病毒介导的眼部病理对IgH分析的限制 主宰了HSV特异性T细胞受体谱系的选择。我们 相信在分子水平上理解这些细节 单纯疱疹病毒免疫应答的免疫调控 它的眼睛将提供更好的洞察更具体 单纯疱疹病毒不当炎症反应的治疗调节。