DELAYED HYPERSENSITIVITY TO HERPES SIMPLEX VIRUS

本项目将继续研究迟发性超敏反应 进一步阐明单纯疱疹病毒(HSV)在小鼠体内的作用 细胞免疫应答在预防HV感染中的作用 建立潜伏期。我们的方法将使用我们已有的模型系统 在动物感染或免疫病毒或免疫的小鼠中产生 病毒蛋白。迟发性超敏反应的评估是通过挑战 耳朵中有病毒或蛋白质的小鼠，并测量耳朵肿胀增加 用工程师的千分尺。保护和延迟在 无保护性小鼠死于致死性单纯疱疹病毒感染的模型系统 10天。鼠标模型提供了一个出色的系统，其中不同 功能性T细胞亚群可以被识别并易于操作。 我们建议从感染细胞中分离出HSV糖蛋白，并对其进行检测 蛋白质，连同化学和/或酶片段，用于其 诱发水解性肝炎和保护性免疫的能力。我们还将合成 与所选择的部分相对应的合成肽 糖蛋白分子，并测试这些多肽对水解性肝病和 保护豁免权。此外，我们还将探索实验方面的内容 某些类型的抑制细胞对HSV的耐受性 先前识别和评估HSV感染小鼠的存在 抑制细胞。我们在这里的目的是确定在活动期间 感染，单纯疱疹病毒诱导抑制细胞，限制免疫反应 从而有利于建立慢性或潜伏性感染。最后我们 建议建立一系列HSV糖蛋白特异性T细胞克隆。 这些克隆将被表征并在体外用于检测细小的 单纯疱疹病毒糖蛋白诱导保护性水解性免疫反应的特异性。 水解酶在预防单纯疱疹病毒感染的免疫保护中的重要性仍然存在 人们对此知之甚少。我们的研究应该为 使用免疫增强剂改进治疗方案的未来发展 和/或主动免疫。

This project will continue to investigate delayed hypersensitivity (DH) to herpes simplex virus (HSV) in mice to further clarify the role of this cell-mediated immune response in protection against HV infection and establishment of latency. Our approach will use a model system we have developed in mice where animals are infected or immunized with virus or viral proteins. Delayed hypersensitivity is assessed by challenging the mice with virus or protein in the ears and measuring increased ear swelling with an engineer's micrometer. Protection and latency is assessed in a model system where nonprotected mice die from lethal HSV infection within 10 days. The mouse model provides an excellent system where different functional T cell subsets can be identified and easiy manipulated. We propose to isolate HSV glycoproteins from infected cells and test these proteins, together with chemical and/or enzymatic fragments, for their ability to induce DH and protective immunity. We will also synthesize synthetic peptides which correspond to selected portions of the glycoprotein molecules and test these peptides for induction of DH and protective immunity. In addition we will explore aspects of experimental tolerance to HSV by characterizing certain types of suppressor cells previously identified and evaluate HSV infected mice for the presence of suppressor cells. Our purpose here is to determine if, during active infection, HSV induces suppressor cells which limit the immune response thus favoring the establishment of chronic or latent infection. Finally we propose to establish a series of HSV glycoprotein-specific T cell clones. These clones will be characterized and used in vitro to examine the fine specificity of the HSV glycoproteins which induce protective DH responses. The importance of DH in immune protection against HSV infection is still poorly understood. Our studies should provide useful information for future development of improved treatment protocols using immunopotentiators and/or active immunization.