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: 3261917
• 负责人: CHARLES STEPHEN FOSTER
• 金额: $ 16.83万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3261917
• 关键词: Alphaherpesvirinae; T lymphocyte; alleles; antibody dependent killer cell; antiviral antibody; cellular pathology; corneal epithelium; corneal stroma; ganglions; genetic strain; helper T lymphocyte; histochemistry /cytochemistry; immunochemistry; immunoglobulin genes; immunoglobulin idiotypes; immunopathology; immunoregulation; immunosuppression; keratitis; laboratory mouse; latent virus infection; linkage mapping; molecular pathology; monoclonal antibody; suppressor T lymphocyte

Herpes simplex keratitis (HSK) is a major problem of epidemic proportions, in spite of the fact that many excellent antiviral drugs exist for treatment of episodes of active HSK. It is clear that both viral and host immune factors collaborate to determine the eventual course of disease expression in any individual with HSK. Unfortunately, huge gaps exist in our understanding of the cellular and molecular events underlying the progression of a corneal epithelial infection with herpes to more devastating corneal stromal disease. We have discovered, using inbred congenic strains of mice, genetically-linked controls which govern the development of HSK which is either predominantly epithelial or predominantly stromal. We have mapped the phenomenon to genes linked to the Igh locus on chromosome XII. Furthermore, in preliminary experiments we have already shown that we can modify the course of disease in those animals which are typically susceptible to the most severe keratitis, through immunologic strategies, so that little to no keratitis at all develops after herpes corneal infection. We propose in this application to study this phenomenon in more detail, with the expectation that understanding it at a cellular and molecular level will enable us to design therapeutic strategies which could modify not only the degree of corneal disease developing after herpes infection, but also the development or continuation of latent infection in the trigeminal ganglion. We plan to study the role of helper T cells, cytotoxic T cells, suppressor T cells, and specific antiherpes antibody and their respective roles in both the protection from pathology and establishment of ganglionic latency, and in the production of pathology and facilitation of latency establishment.

单纯疱疹病毒性角膜炎（HSK）是一种流行性的主要问题， 尽管存在许多优秀的抗病毒药物， 治疗活动性HSK发作。 很明显，病毒和宿主 免疫因素共同决定疾病的最终进程 HSK的表达。 不幸的是， 我们对细胞和分子事件的理解， 疱疹性角膜上皮感染的进展 毁灭性的角膜基质疾病 我们发现，利用近亲繁殖 小鼠的同类品系，控制 HSK的发展主要是上皮性的， 主要是基质。 我们已经将这一现象定位到与以下基因相关的基因上： 染色体XII上的Igh基因座。 此外，在初步实验中， 我们已经证明，我们可以改变疾病的进程， 通常易患最严重角膜炎的动物， 通过免疫策略， 在角膜疱疹感染后出现。 在本申请中，我们建议更详细地研究这种现象， 希望能从细胞和分子水平上理解它， 水平将使我们能够设计治疗策略， 不仅是疱疹感染后角膜疾病发展的程度， 而且还可以防止在患者中潜伏感染的发展或持续。 三叉神经节 我们计划研究辅助性T细胞的作用， 细胞毒性T细胞、抑制性T细胞和特异性抗疱疹抗体， 它们各自在预防病理学和 神经节潜伏期的建立，以及病理学和 促进潜伏期建立。