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: 3261920
• 负责人: CHARLES STEPHEN FOSTER
• 金额: $ 23.57万
• 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/3261920
• 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.

单纯疱疹性角膜基质炎（HSK）是一个毁灭性的问题， 存在完全令人满意的疗法。 HSK的免疫发病机制是 不完全理解。 我们已经建立并研究了一种小鼠模型， HSK和已经显示出强烈影响的基因在或紧密连锁 12号染色体上的IgH免疫球蛋白同种异型基因座 角膜对疱疹的免疫/炎症反应。 的 淋巴细胞介导和抗体介导反应之间的相互作用 保护免受炎症性角膜破坏， 复杂，但我们的研究结果表明， 在协调保护与 病理学发展围绕免疫调节控制， 来源于Igh-1编码的产物， 12号染色体 我们的研究使我们假设抗体 抗单纯疱疹病毒抗体之间的独特型结构域差异 HSV特异性T细胞受体库的应答和/或差异 在Igh-1不同同类小鼠中， 细胞募集和临床上明显病理学的发展， 角膜病变的一种形式。 我们打算进一步分析高- 1限制HSV介导的眼部病理学分析IgH-1， 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， 对单纯疱疹病毒免疫应答的免疫调节控制 因为它是在眼中看到的，将提供更好的洞察力， 治疗性调节对HSV的不适当炎症反应。