MOUSE HEPATITIS VIRUS-ASSOCIATED IMMUNE DYSFUNCTION

小鼠肝炎病毒相关的免疫功能障碍

• 批准号: 3421494
• 负责人: ABIGAIL L SMITH
• 金额: $ 16.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3421494
• 关键词: B lymphocyte; CD4 molecule; CD8 molecule; T lymphocyte; animal viral hepatitis; antibody formation; antiviral antibody; athymic mouse; cellular immunity; communicable disease control; epizootiology; helper T lymphocyte; immunopathology; immunotherapy; interferons; interleukin 4; laboratory mouse; leukocyte activation /transformation; macrophage; murine hepatitis virus; natural killer cells; newborn animals; tissue /cell culture; virus antigen

Mouse hepatitis virus (MHV) infection of laboratory mice occurs at high prevalence and impacts heavily on many biomedical disciplines in which mice are commonly used. Infection of lymphocyte donors with MHV results in T cell dysfunction, as reflected by in vitro proliferation and cytokine production. However, the role of cytokines in the pathogenesis of MHV infection after exposure of mice by natural routes has not been addressed. Once the role of these molecules has been firmly established, efforts will be made to identify the cell type(s) secreting cytokines and the cell type(s) upon which they act. The long-term goal is the development of rational strategies for control and prevention of enzootic MHV in laboratory mouse colonies. The specific aims of the proposed research are: 1. to characterize further the role of cytokines in MHV pathogenesis, using cytokine immunotherapy or induction methods and cytokine deletion, and 2. to identify the cell types producing beneficial cytokines as well as those that are activated by these soluble mediators. The objective of the current proposal is to test the hypothesis that certain cytokines released by activated T cells, as well as other cell types, may mediate benign outcome of infection with MHV. Interferon gamma and interleukin 4 are the molecules of primary interest. Pilot data suggest that effector function of CD4+ T cells may be associated with pathology and negative outcome of MHV infection. These two aspects of T cell biology are difficult to separate; however, drug- and/or antibody-induced cell deletion combined with cytokine immunotherapy will begin to suggest whether our hypothesis has merit. The availability of genetically defined mice, recombinant cytokines, monoclonal antibodies reactive with these molecules and cell-specific drugs renders an approach to the in vivo interactions of virus and the immune system feasible.

实验室小鼠的小鼠肝炎病毒（MHV）感染发生在高处 患病率并对许多生物医学学科产生重大影响 通常使用。 用MHV感染淋巴细胞供体导致T 细胞功能障碍，如体外增殖和细胞因子所反映的 生产。 但是，细胞因子在MHV发病机理中的作用 尚未解决小鼠暴露后的感染。 一旦这些分子的作用牢固确立，努力将 制作以识别细胞类型分泌细胞因子和细胞 他们采取行动的类型。 长期目标是发展 控制和预防Enzootic MHV的理性策略 实验室小鼠菌落。 拟议研究的具体目的是：1。进一步表征 细胞因子在MHV发病机理中的作用，使用细胞因子免疫疗法或 诱导方法和细胞因子缺失，以及2。 产生有益的细胞因子以及这些因子激活的细胞因子 可溶性介体。 当前提议的目的是检验以下假设。 激活的T细胞以及其他细胞释放的某些细胞因子 类型可以介导MHV感染的良性良性结果。 干扰素伽玛 白介素4是主要感兴趣的分子。 试点数据 表明CD4+ T细胞的效应子功能可能与 MHV感染的病理和负面结果。 T的这两个方面 细胞生物学很难分离。但是，药物和/或 抗体诱导的细胞缺失与细胞因子免疫疗法结合 开始暗示我们的假设是否有价值。 可用性 遗传定义的小鼠，重组细胞因子，单克隆抗体 用这些分子和细胞特异性药物进行反应使方法 病毒与免疫系统的体内相互作用可行。