IMMUNOLOGY AND GENETICS OF HERPES SIMPLEX KERATITIS

单纯疱疹病毒性角膜炎(HSK)是流行比例的主要问题， 尽管有许多优秀的抗病毒药物存在于 单纯疱疹病毒性角膜炎活动期的治疗。很明显，无论是病毒还是宿主 免疫因素共同决定疾病的最终进程 在任何患有HSK的个体中都有表达。不幸的是，存在着巨大的差距 我们对细胞和分子事件的理解 合并疱疹的角膜上皮感染进展到更多 毁灭性的角膜间质疾病。我们发现，使用近亲交配 小鼠的同源品系，基因连锁的对照 以上皮性为主的单纯疱疹病毒性角化症 以基质为主。我们已经将这一现象与基因联系起来 12号染色体上的IgH基因座。此外，在初步实验中， 我们已经证明，我们可以改变这些患者的病程 这些动物通常容易患上最严重的角膜炎， 通过免疫策略，所以很少或根本没有角膜炎 在角膜疱疹感染后发生。 在本申请中，我们建议更详细地研究这一现象， 期望从细胞和分子的角度来理解它 水平将使我们能够设计治疗策略，这可能会改变 不仅是疱疹感染后角膜病变的程度， 也会导致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 它们各自在保护动物免受病理和 神经节潜伏期的建立，以及在病理和 促进潜伏期的建立。

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.