IMMUNOLOGICAL CONTROLS IN HSV LATENCY AND REACTIVATION

HSV 潜伏期和再激活的免疫学控制

• 批准号: 3453788
• 负责人: STEPHEN ROBERT JENNINGS
• 金额: $ 9.25万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453788
• 关键词: Alphaherpesvirinae; Herpesviridae disease; T lymphocyte; antibody dependent killer cell; helper T lymphocyte; histocompatibility antigens; immunoregulation; latent virus infection; microorganism immunology; monoclonal antibody; virus replication

The overall aim of this proposal will be to determine the role of individual phenotypically and functionally defined T lymphocte subpopulations in the control of three distinct stages of the host-virus relationship following infection with herpes simplex virus (HSV). The stages to be studied will be (i) the clearance of virus from the primary site of infection, (ii) the establishment of latent infection in neurons of local sensory ganglia, and (iii) the reactivation of virus from the latent state. The first objective will be to determine the rate of appearance and frequency of precursors of immunologically functional HSV-specific helper and cytotoxic T lymphocytes in local lymphoid tissue following a local infection with HSV, and to extend the study to immunized mice responding to a secondary infection. This will be assessed in two strains of inbred mice which exhibit different levels of innate resistance to HSV infection. C57BL/6 (H-2b) mice are relatively resistant to infection with HSV, while BALB/c (H-2d) mice are moderately sensitive. Innate resistance is genetically determined, and has been shown to have an immunological basis in the T lymphocyte-mediated component of the immune response. This suggests that the sensitive strains may have a fundamental immunological deficiency that precludes the successful initial control of HSV multiplication and dissemmination. By comparing the early T lymphocyte repsonse in these two strains, it will be possible to determine whether an underlying T lymphocyte-mediated response is responsible for this observation. The second objective will be to determine the role of the T lymphocyte response in the control of HSV multiplication and clearance from the primary site of infection, the establishment of latency and subsequent reactivation of HSV from the latent state. This will be studied by the adoptive transfer of phenotypically and functionally defined HSV-specific T lymphocyte subsets to naive recipients, and by selective in vivo depletion of these subsets by treatment with monoclonal antibodies specific for differentiation isoantigens associated with each funcitonal subset. The third objective will be to determine the role of HSV viral glycoproteins involved, and the mode in which these components are presented to the HSV-specific T lymphocytes that results in an effective response.

本建议的总体目标是确定以下方面的作用： 单个表型和功能确定的T淋巴细胞 控制宿主病毒三个不同阶段的亚群 单纯疱疹病毒（HSV）感染后的关系。 的 研究的阶段将是（i）从原发灶中清除病毒 感染部位，（ii）在神经元中建立潜伏感染， 局部感觉神经节，和（iii）病毒从潜伏的 状态 第一个目标是确定出庭率， 免疫功能性HSV特异性辅助细胞前体的频率 局部淋巴组织中的细胞毒性T淋巴细胞 感染HSV，并将研究扩展到免疫小鼠， 继发性感染 这将在两种近交系小鼠中进行评估 其表现出不同水平的对HSV感染的先天抗性。 C57 BL/6（H-2b）小鼠对HSV感染具有相对抗性，而 BALB/c（H-2d）小鼠是中等敏感的。 天生的抵抗力是 基因决定，并已被证明具有免疫学基础 免疫反应中T淋巴细胞介导的成分。 这 表明敏感菌株可能具有基本的免疫学特性， 一种妨碍HSV初步控制成功的缺陷 繁殖和传播。 通过比较早期T淋巴细胞 在这两种菌株中，将有可能确定 潜在的T淋巴细胞介导的反应是负责这一点 观察. 第二个目标是确定T的作用 淋巴细胞反应在控制HSV增殖和清除 感染的主要部位，潜伏期的建立和随后的 HSV从潜伏状态的再活化。 这将由 表型和功能确定的HSV特异性T细胞过继转移 淋巴细胞亚群，并通过选择性体内耗竭 这些亚群的治疗与单克隆抗体特异性 与每个功能亚群相关的分化同种抗原。 的 第三个目标是确定HSV病毒糖蛋白的作用 所涉及的，以及这些组件呈现给 HSV特异性T淋巴细胞，导致有效的反应。