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: 3261916
• 负责人: CHARLES STEPHEN FOSTER
• 金额: $ 16.42万
• 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/3261916
• 关键词: Alphaherpesvirinae; T lymphocyte; alleles; antiviral antibody; cellular pathology; corneal epithelium; corneal stroma; ganglions; genetic strain; helper T lymphocyte; histochemistry /cytochemistry; immunochemistry; immunoglobulin genes; immunopathology; immunoregulation; immunosuppression; keratitis; 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.

单纯疱疹性角膜炎（HSK）是一个主要的流行病问题，