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: 3261913
• 负责人: CHARLES STEPHEN FOSTER
• 金额: $ 20万
• 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/3261913
• 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.

疱疹性基质角膜炎 (HSK) 是一个毁灭性的问题，目前尚无有效的治疗方法。 存在完全令人满意的治疗方法。 HSK的免疫发病机制是 不完全理解。 我们制作并研究了小鼠模型 HSK 并已显示出该基因的强大影响力或密切相关 12 号染色体上的 Igh 免疫球蛋白同种异型位点 对角膜中遇到的疱疹的免疫/炎症反应。 这 淋巴细胞介导的反应和抗体介导的反应之间的相互作用 防止炎症性角膜破坏的产生是 复杂，但我们的研究结果表明，关键 调解保护与保护之间平衡的决定因素 病理学的发展围绕着免疫调节控制， 源自 Igh-1 和紧密相连的基因编码的产物 12号染色体。我们的研究使我们得出这样的假设：抗体 抗单纯疱疹抗体之间的独特型结构域差异 HSV 特异性 T 细胞受体库的反应和/或差异 在 Igh-1 不同的同源小鼠中导致细胞反应的差异， 细胞募集和临床明显病理学的发展 角膜病的形式。 我们打算进一步分析 Igh- 现象 1 HSV 介导的眼部病理学对 Igh- 分析的限制 控制 HSV 特异性 T 细胞受体库的选择。 我们 相信在分子水平上理解 对单纯疱疹病毒免疫反应的免疫调节控制 正如在眼睛中看到的那样，可以更好地了解更具体的情况 对 HSV 的不适当炎症反应的治疗调节。